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Vishwanath R, Biswas A, Modi U, Gupta S, Bhatia D, Solanki R. Programmable short peptides for modulating stem cell fate in tissue engineering and regenerative medicine. J Mater Chem B 2025; 13:2573-2591. [PMID: 39871657 DOI: 10.1039/d4tb02102a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2025]
Abstract
Recent advancements in tissue engineering and regenerative medicine have introduced promising strategies to address tissue and organ deficiencies. This review highlights the critical role of short peptides, particularly their ability to self-assemble into matrices that mimic the extracellular matrix (ECM). These low molecular weight peptides exhibit target-specific activities, modulate gene expression, and influence cell differentiation pathways. They are stable, programmable, non-cytotoxic, biocompatible, biodegradable, capable of crossing the cell membrane and easy to synthesize. This review underscores the importance of peptide structure and concentration in directing stem cell differentiation and explores their diverse biomedical applications. Peptides such as Aβ1-40, Aβ1-42, RADA16, A13 and KEDW are discussed for their roles in modulating stem cell differentiation into neuronal, glial, myocardial, osteogenic, hepatocyte and pancreatic lineages. Furthermore, this review delves into the underlying signaling mechanisms, the chemistry and design of short peptides and their potential for engineering biocompatible materials that mimic stem cell microenvironments. Short peptide-based biomaterials and scaffolds represent a promising avenue in stem cell therapy, tissue engineering, and regenerative medicine.
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Affiliation(s)
- Rohan Vishwanath
- School of Life Science, Central University of Gujarat, Gandhinagar-382030, India
| | - Abhijit Biswas
- Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India.
| | - Unnati Modi
- Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India.
| | - Sharad Gupta
- Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India.
| | - Dhiraj Bhatia
- Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India.
| | - Raghu Solanki
- Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India.
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Guarino M. Immunohistochemical Distribution of Basement Membrane Type IV Collagen and Laminin in Synovial Sarcoma. TUMORI JOURNAL 2018; 79:427-32. [PMID: 8171745 DOI: 10.1177/030089169307900612] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Aims To investigate the distribution of basement membrane components type IV collagen and laminin in synovial sarcomas. Methods Paraffin sections from four synovial sarcomas were studied by the peroxidase-antiperoxldase procedure using specific antibodies to type IV collagen and laminin. Results Type IV collagen and laminin immunoreactivity was confined around epithelial areas in biphasic tumors. Several interruptions and discontinuities of the linear basement membrane profile were seen in sites of transition between mesenchymal and epithelial tissue. Moreover, a spot-like immunoreactivity was often observed in the spindle cell component of biphasic tumors. Monophasic tumors were either negative or showed a pericellular staining for both type IV collagen and laminin. Conclusions The distribution of basement membrane components is clearly related to the formation of epithelial elements in biphasic synovial sarcoma. The spot-like immunoreactivity of the spindle cell component, and the basement membrane interruptions at the boundary between mesenchymal and epithelial tissue, are both consistent with early basement membrane formation by developing epithelium. These findings support the concept that synovial sarcomas are basically soft tissue carcinosarcomas and that the epithelial component of the tumors develops by conversion of mesenchyme to epithelium.
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Affiliation(s)
- M Guarino
- Department of Anatomical Pathology, Hospital of Treviglio, Bergamo, Italy
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Markovic-Lipkovski J, Brasanac D, Müller GA, Müller CA. Cadherins and Integrins in Renal Cell Carcinoma an Immunohistochemical Study. TUMORI JOURNAL 2018; 87:173-8. [PMID: 11504373 DOI: 10.1177/030089160108700312] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Aims and Background The aim of this study was to determine the expression of cadherins and integrins in renal cell carcinoma (RCC) and their relationship with tumor morphology and TNM status. Methods Cadherin and integrin expression was investigated using an indirect immunoperoxidase technique, applying antibodies to E-, N-, P- and VE-cadherin and to α1, α2, α3, α4, α5, α6 and αv integrin subunits. Correlation of semiquantitatively scored adhesion molecule levels with histopathological parameters (cytology, growth pattern, nuclear grade) and TNM status was performed for 24 RCCs (17 clear cell, 3 granular, 3 spindle cell and 1 chromophobe cell type according to the WHO classification). Results E-cadherin and N-cadherin were present in most cases (88% and 67%, respectively) and were usually coex-pressed. T3 RCCs displayed higher E-cadherin and N-cadherin levels than T1/T2 tumors regardless of tumor grade, suggesting that impairment of their function might exist without actual loss from tumor cells. P-cadherin was found focally in two RCCs only, while VE-cadherin was present on stromal vessel endothelium in five tumors, showing no differences with regard to cell type, growth pattern, tumor grade or TNM status. All integrins were present in the studied RCCs (ranging from 12% for α5 to 79% for α3), including those that are normally absent from adult kidney tissue (α4 and α5). Tumors of higher grade showed increased αv and decreased α6 levels, while RCCs with metastases less often showed diffuse α3 presence and never expressed α5 integrin. Conclusions Our results suggest that the level of expression of N-cadherin and some integrins (most notably α3, α6, and α5) is associated with the capacity of RCC for local and distant spread, regardless of tumor grade.
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Wu N, Gidrol X. The wind rose of human keratinocyte cell fate. Cell Mol Life Sci 2014; 71:4697-702. [PMID: 25326028 PMCID: PMC4233109 DOI: 10.1007/s00018-014-1758-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 10/04/2014] [Accepted: 10/09/2014] [Indexed: 12/27/2022]
Abstract
Extensive efforts have been made to understand the molecular actors that control epithelial cell fate. Although pieces of information have been obtained from single-gene function investigations, the entire picture of the molecular mechanisms involved in the regulation of epithelial homeostasis is still mysterious. Growing data indicate that gene networks rather than single “master” genes dictate cell fate. In an attempt to characterize such gene networks, we have been investigating the human keratinocyte proliferation and differentiation genes that act downstream of the transcription factor p63, a major regulator of epidermal homeostasis. We identified two networks: the cell cycle network that controls cell proliferation and the keratinocyte cell fate network. Through further analysis of the existing data on epithelial tumorigenesis and induced pluripotent stem cells, we propose a wind rose model of cell fate that is based on a balance between these two different networks that ultimately control human keratinocyte fate and epidermal homeostasis.
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Affiliation(s)
- Ning Wu
- Univ. Grenoble Alpes, iRTSV-BGE, 38000, Grenoble, France,
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Yu Y, Kuebler J, Groos S, Metzelder M, Kurpanik S, Ure BM, Vieten G. Carbon dioxide modifies the morphology and function of mesothelial cells and facilitates transepithelial neuroblastoma cell migration. Pediatr Surg Int 2010; 26:29-36. [PMID: 19847444 DOI: 10.1007/s00383-009-2503-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The response of mesothelial cells to surgical trauma and bacterial contamination is poorly defined. We have recently shown that CO(2) pneumoperitoneum increases systemic metastasis of neuroblastoma cells in a murine model. Thus, we hypothesized that CO(2) alters the morphology and function of mesothelial cells and facilitates transmesothelial tumor cell migration. MATERIALS AND METHODS Murine mesothelial cells were exposed to 100% CO(2) and 5% CO(2) as control. Scanning electron microscopy (SEM) investigations, as well as LPS-induced granulocyte-colony stimulating factor (G-CSF) production and mitochondrial activity (MTT assay) were measured. Transmesothelial migration of neuroblastoma cells (Neuro2a) was determined using a transwell chamber system. RESULTS CO(2) incubation was associated with a significant destruction of the microvillar formation in SEM. Migration studies showed that the barrier function of the mesothelial monolayer decreased. A significantly increased migration of neuroblastoma cells was identified after 100% CO(2) exposure (P < 0.05). Although the conversion of MTT as an indicator of mitochondrial activity was only slightly and not significantly reduced after CO(2) incubation, the release of G-CSF induced by LPS was completely blocked during the incubation with 100% CO(2) (P < 0.05). The capacity of G-CSF release recovered after the incubation. CONCLUSION We observed that peritoneal mesothelial cells lose their typical cell morphology by CO(2) incubation, which is accompanied by facilitated migration of neuroblastoma cells. Moreover, the synthesis of immunological factors is blocked, but this effect is not long lasting. These mechanisms may explain an increased metastasis rate of neuroblastoma cells after CO(2) pneumoperitoneum, which was recently observed in a murine model.
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Affiliation(s)
- Yi Yu
- Department of Pediatric Surgery, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
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Poulopoulos A, Belazi M, Epivatianos A, Velegraki A, Antoniades D. The role of candida in inflammatory papillary hyperplasia of the palate. J Oral Rehabil 2007; 34:685-92. [PMID: 17716268 DOI: 10.1111/j.1365-2842.2007.01758.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The objective of this study was to investigate the expression by immunohistochemistry of the major basement membrane (BM) components (laminin, collagen type IV, fibronectin) in specimens from the palatal mucosa lesions of patients with complete dentures and diagnosis of inflammatory papillary hyperplasia of the palate (IPHP). Furthermore to evaluate the potential role of candidal infection in patients with IPHP. Biopsies of palatal mucosa were obtained from patients with IPHP, generally healthy/orally healthy patients with dentures, and healthy subjects. Immunohistochemical studies performed with specific antibodies to BM proteins. Scrapings and swaps of oral lesions from all patients and control groups were taken from the palate, and Candida species colonization was assessed with mycology tests. Immunohistochemical expression of BM components revealed thin linear staining in the BM of healthy palatal mucosa. In IPHP discontinuities or disruptions in BM were observed at the interface between epithelium and the underlying connective tissue in the areas of severe inflammatory response. Our findings suggest an interaction between the expression of BM components and Candida involvement in the development of IPHP, a disorder involving inflammatory reaction and modification of soft tissues.
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Affiliation(s)
- A Poulopoulos
- Department of Oral Medicine and Maxillofacial Pathology, Dental School of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece.
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Abstract
Sulphur mustard is a vesicant (blistering agent), which produces chemical burns with widespread blistering. It was used extensively as a chemical warfare agent in the First World War, and has allegedly been employed in a number of conflicts since then, most recently by Iraq against Iran (1984-1987). The potential further use of mustard in military conflicts and by terrorists remains a significant threat that if realised in practice would result in a large number of casualties with severely incapacitating, partial thickness burns. Such injuries clearly present a huge potential wound care problem. The development and healing of mustard-induced cutaneous injuries has not only been observed in human casualties, but has been studied recently at the microscopic and ultrastructural levels in several animal models. Vesication generally begins on the second day after exposure, and may progress for up to 2 weeks. Wound healing is considerably slower than for a comparable thermal burn, and patients often require extended hospital treatment. The current management strategy is essentially symptomatic and supportive. Recently, two techniques for removing damaged tissue and improving wound healing have been investigated. Mechanical dermabrasion and laser debridement ('lasablation') both produced an increased rate of wound healing in animal models, and may be of benefit in a clinical context.
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Affiliation(s)
- Paul Rice
- Biomedical Sciences Department, Dstl Porton Down, Salisbury, UK
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Zhou YN, Xu CP, Han B, Li M, Qiao L, Fang DC, Yang JM. Expression of E-cadherin and β-catenin in gastric carcinoma and its correlation with the clinicopathological features and patient survival. World J Gastroenterol 2002; 8:987-93. [PMID: 12439911 PMCID: PMC4656404 DOI: 10.3748/wjg.v8.i6.987] [Citation(s) in RCA: 80] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. We evaluated the expression pattern of E-cadherin and β-catenin in gastric carcinoma and dysplasia and analyzed their relationship with tumor clinicopathological features and patient survival.
METHODS: Immunohistochemical staining of E-cadherin and β-catenin was performed from paraffin specimens of 163 gastric carcinomas, 44 gastric mucosal dysplasia, and 25 intestinal metaplasia, 28 atrophic gastritis and 12 healthy controls.
RESULTS: Normal membrane staining was observed in intestinal metaplasia, atrophic gastritis and control biopsy specimens for E-cadherin and β-catenin. 36% and 16% of gastric dysplasia were stained abnormally for E-cadherin and β-catenin respectively. Abnormal expression of E-cadherin and β-catenin was demonstrated in 46% and 44% of gastric carcinoma respectively. Abnormal expression of E-cadherin and β- catenin occurred more significantly in Borrmann III/IV than in Borrmann I/II type (P < 0.005, respectively). A significantly higher proportion of signet-ring, mucinous and tubular adenocarcinomas were abnormally expressed for E-cadherin and β-catenin as compared with papillary adenocarcinomas (χ2 = 8.47, P < 0.005, and χ2 = 7.05, P < 0.01, respectively). Morever, abnormal E-cadherin and β-catenin staining occurred more frequently in diffuse than in intestinal type of tumor (χ2 = 18.18 and 17.79, P < 0.005, respectively). There was a significant correlation between abnormal β-catenin expression and positive lymph node metastasis. A survival advantage was noted in tumors retaining normal membranous expression of β-catenin, independent of type, grade, or stage of the disease (P < 0.0005).
CONCLUSION: Abnormal expression of the E-cadherin-catenin complex occurs frequently in gatric carcinoma, closely related to its histogenesis. Abnormal expression of the E-cadherin- catenin complex in gastric dysplasia may be an early event in the tumorigenesis. The close correlation with poor survival suggests that abnormal β-catenin may be a useful prognostic marker.
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Affiliation(s)
- Yong-Ning Zhou
- Department of Gastroenterology, Southwest Hospital, the Third Millitary Medical University, Chongqing, 400038, China.
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Restucci B, Maiolino P, Papparella S, De Vico G. Expression of beta1 integrin in relation to histological features in normal and neoplastic canine testicles. J Comp Pathol 2000; 123:164-70. [PMID: 11032670 DOI: 10.1053/jcpa.2000.0410] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The expression of the beta1 common chain of the VLA integrin subfamily was evaluated immunohistochemically in a series of five normal and 30 neoplastic canine testicles. The tumours, consisting of seminomas or Sertoli cell tumours, were classified according to WHO criteria as intraductal without signs of invasion, intraductal with signs of invasion, or diffuse. Expression of beta1 integrin decreased progressively from intraductal tumours without signs of invasion, to the diffuse type, in which immunolabelling was generally absent. In a few cases of diffuse neoplasia, groups of neoplastic cells exhibited strong positivity that was not restricted to the basal pole of the cell membrane. These results suggest that the expression of beta1 integrin was related to the histological tumour type, possibly reflecting a specific requirement for a reduction in integrin by neoplastic cells with infiltrative and metastatic potential.
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Affiliation(s)
- B Restucci
- Dipartimento di Patologia e Sanità Animale-Settore Anatomia Patologica Facoltà di Medicina Veterinaria, Università "Federico II", Naples, Italy
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10
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Rice P, Brown RF, Lam DG, Chilcott RP, Bennett NJ. Dermabrasion--a novel concept in the surgical management of sulphur mustard injuries. Burns 2000; 26:34-40. [PMID: 10630317 DOI: 10.1016/s0305-4179(99)00096-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Since its first use on the battlefields of Northern France during the First World War (1914-1918), sulphur mustard has remained a significant chemical threat to military forces around the world. Progress towards an effective treatment for these injuries has been slow due to the lack of suitable animal models upon which to study the toxicology and pathology. However, porcine and human skin are similar in structure and exposures to sulphur mustard vapour have been performed on porcine models to define the development and subsequent resolution of mustard-induced skin injuries. Yucatan miniature (n = 12) and large white (n = 6) pig models were used to assess the usefulness of mechanical dermabrasion in accelerating the naturally slow rate of healing of sulphur mustard vapour-induced injuries to the skin. Burn injuries underwent debridement at 4 days post-exposure and the resulting lesions were assessed at various time points up to 8 weeks post-abrasion. Rates of re-epithelialisation were accelerated in the dermabrasion (treated) vs the control (untreated) group by up to a factor of three (ANOVA: p = .0196, Yucatan; p = 0.165, large white pig). It was concluded that dermabrasion of sulphur mustard burns is a valuable procedure in the surgical management of these injuries.
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Affiliation(s)
- P Rice
- Biomedical Sciences Department, DERA, CBD Porton Down, Salisbury, Wiltshire, UK
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11
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Abstract
Studies performed in the past in our laboratory have detailed the development of sulphur mustard lesions in the domestic, white pig using small glass chambers to achieve saturated vapour exposure under occluded conditions. We have now used this experimental model to produce cutaneous lesions for detailed histopathological studies following challenge with lewisite. Histological examination of resulting lesions have revealed that although the overall pattern of lesion development is similar to that seen following mustard challenge, the time-course of cellular events is very much compressed. The epidermis showed focal basal cell vacuolation with associated acute inflammation as early as one hour postexposure. Coagulative necrosis of the epidermis and papillary dermis was complete by 24 hours and followed the appearance of multiple coalescent blisters between six and 12 hours post-exposure. At 48 hours, the lesions were full thickness burns with necrosis extending into the deep subcutaneous connective and adipose tissues. The study of lesions beyond 24 hours revealed early epithelial regeneration at the wound edge. The overall spontaneous healing rate of these biologically severe lesions was significantly faster than comparable sulphur mustard injuries and probably reflected a lack of alkylation of DNA and RNA.
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Affiliation(s)
- P Rice
- Biomedical Science Department, CBD Porton Down, Salisbury, UK
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12
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Glüer S, Zense M, von Schweinitz D. Cell adhesion molecules and intermediate filaments on embryonal childhood tumors. Pathol Res Pract 1998; 194:773-80. [PMID: 9842636 DOI: 10.1016/s0344-0338(98)80067-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
We describe the expression of 18 different cell adhesion molecules, intermediate filaments and Ki-67 antigen in embryonal childhood tumors. 5 microns frozen sections from 15 nephroblastomas, 13 neuroblastomas, six rhabdomyosarcomas, one Ewing sarcoma and one pulmonary blastoma were analyzed by the alkaline phosphatase anti-alkaline phosphatase (APAAP) method using murine monoclonal antibodies. All tumors exhibited high proliferation rates as did, surprisingly, the nephroblastoma specimens despite pre-treatment with chemotherapy. Polysialylated NCAM was demonstrated on all tumor types, but Ewing sarcoma and expression correlated inversely with cell differentiation. In contrast, E-cadherin was present solely on tubulus like cells in nephroblastomas. This cell type showed a coexpression of cytokeratin and vimentin, giving evidence of its intermediate position between the mesenchyme and epithelium. In neuroblastomas, CD44s (hyaluronate receptor) expression was increased with cell differentiation. ICAM-1, VCAM-1 and E-selectin were mostly expressed in regressive areas of pretreated nephroblastoma specimens where a considerable infiltration of leukocytes was noted as well. Since endothelial and leukocyte adhesion molecules were distinctly less expressed in all other tumors investigated, these findings may indicate immunological processes as a consequence of or as supplement to the chemotherapeutical effect on nephroblastoma cells. Integrin receptors were not found on the surface of tumor cells, and therefore, at least those investigated seem to be of secondary importance to the biology of the tumors studied herein. In conclusion, our investigations demonstrate that, besides achieving a secure and prompt differentiation between various embryonal tumors, applying the panel of monoclonal antibodies proposed herein gives interesting insights into the histogenesis, biology and metastatic potential of pediatric malignancies.
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Affiliation(s)
- S Glüer
- Department of Pediatric Surgery, Medical School Hannover, Germany.
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Abstract
Different adhesion molecules are implicated in the pathogenesis in glomerulonephritis. Leukocyte adhesion molecules play a critical role in causing renal damage in a variety of glomerulonephritic conditions. In order to understand the mechanisms by which distinct adhesion molecules are involved in human glomerulonephritis, it is necessary to have an overview of their function in maintenance of tissue architecture, morphogenesis, immunosurveillance, inflammation, tumor growth, etc. Thus, this review addresses the role of cadherins, selectins, integrins, and members of the immunoglobulin supergene family in developing, normal, and diseased kidney with special attention to glomerulonephritis and possible new therapeutic approaches.
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Affiliation(s)
- G A Müller
- Department of Nephrology and Rheumatology, Georg August University, Göttingen, Germany
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Shino Y, Watanabe A, Yamada Y, Tanase M, Yamada T, Matsuda M, Yamashita J, Tatsumi M, Miwa T, Nakano H. Clinicopathologic evaluation of immunohistochemical E-cadherin expression in human gastric carcinomas. Cancer 1995; 76:2193-201. [PMID: 8635021 DOI: 10.1002/1097-0142(19951201)76:11<2193::aid-cncr2820761104>3.0.co;2-2] [Citation(s) in RCA: 73] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND E-cadherin plays a crucial role in cell-cell adhesion in epithelial tissues. Recent studies have shown a correlation between decreased E-cadherin expression and cancer cell detachment. METHODS The expression of E-cadherin was immunohistochemically analyzed using antihuman E-cadherin antibody in 121 cases of human gastric carcinoma. RESULTS In noncancerous areas, the epithelial cells, including those with intestinal metaplasia, were stained positively in the plasma membrane. In contrast, E-cadherin expression of the cancer cells varied from case to case in primary and secondary sites. Tumors with a decrease in E-cadherin occurred significantly more frequently in undifferentiated adenocarcinoma (P < 0.05) and scirrhous type (P < 0.01). The rate of E-cadherin-negative tumors was higher in patients with peritoneal metastasis (P < 0.01) or in those with distant lymph node metastasis (P < 0.01), though the tumors with liver metastasis had relatively positive E-cadherin expression. Patterns of initial recurrence had similar results. Reduction or loss of E-cadherin expression correlated with shorter survival in patients after curative operation regardless of stage of disease. CONCLUSIONS The decreased E-cadherin expression correlates with dedifferentiation, infiltrative tumor growth, distant metastasis, and poor survival for patients with gastric carcinoma. Thus, immunohistochemical study of E-cadherin may have clinicopathologic value for patients with gastric carcinoma.
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Affiliation(s)
- Y Shino
- First Department of Surgery, Nara Medical University, Kashihara, Japan
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15
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Abstract
Loss of cell adhesion is a critical event in the development of tumour invasiveness and metastases. Although loss of cadherin expression has been demonstrated to be associated with increased invasiveness and metastatic potential in some tumours, others, including renal carcinoma, show no such correlation. The aim of this study was to demonstrate that cell adhesion could be lost in phorbol ester-treated renal epithelial cells and renal tumour cells without loss of A-CAM expression. The model used has been shown previously to mimic changes that occur in the progression of renal carcinoma. We found that A-CAM expression persists on the lateral surfaces of phorbol ester-treated cells even though these cells lose cell-cell adhesion. Similar findings were seen in renal carcinoma cells in culture. We conclude that loss of cell adhesion between tumour cells may other either by loss of cadherins or as a result of loss cadherin function occurring as a consequence of cell transformation.
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Affiliation(s)
- M O'Donnell
- Department of Pathology, University of Edinburgh, U.K
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Patriarca C, Roncalli M, Gambacorta M, Cominotti M, Coggi G, Viale G. Patterns of integrin common chain beta 1 and collagen IV immunoreactivity in hepatocellular carcinoma. Correlations with tumour growth rate, grade and size. J Pathol 1993; 171:5-11. [PMID: 7693901 DOI: 10.1002/path.1711710104] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Thirty cases of hepatocellular carcinoma (HCC) were investigated immunocytochemically for expression of beta 1 integrin molecule and of collagen IV. Immunoreactivity was related to the tumour proliferation index, as detected by PCNA immunostaining, and to tumour size and grade. Membrane beta 1 integrin immunoreactivity was detected in the neoplastic cells of all cases, though two different staining patterns were clearly recognized. In 14 cases, beta 1 integrin immunoreactivity was confined to the cell-stroma interface, showing the same polarized pattern as the non-neoplastic cell counterpart. This staining pattern was associated significantly (P < 0.0001) with low PCNA labelling (i.e. less than 20 per cent of neoplastic cells showing nuclear immunostaining. Conversely, 16 cases showed non-polarized pericellular beta 1 integrin immunostaining. This staining pattern was significantly associated (P < 0.0001) with high PCNA labelling (more than 20 per cent of immunoreactive cells) and with tumour size greater than 4 cm in diameter (P < 0.0001). beta 1 Integrin, collagen IV, and PCNA immunoreactivities, however, did not correlate with the histological grade. The data emphasize that neoplastic progression of HCCs may be correlated with an aberrant expression of adhesion molecules and with a disruption of the collagen IV complement of basal membranes.
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Affiliation(s)
- C Patriarca
- II Department of Pathology, University of Milan, School of Medicine, Italy
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Rahilly MA, Fleming S. Metabolic requirements for phorbol ester-induced cytoskeletal changes in renal epithelium. J Pathol 1993; 169:439-43. [PMID: 8501541 DOI: 10.1002/path.1711690409] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Alteration of the cytoskeleton and cell-substratum adhesion are important in the progression of renal carcinoma. We have previously shown that treatment of normal human renal epithelium with phorbol esters mimics the changes seen in renal carcinoma cells. In this study we have demonstrated that the phorbol ester-induced cytoskeletal reorganization is inhibited in the presence of deoxyglucose but not by cycloheximide. We have also shown that treatment of cells with cytochalasin B results in the formation of immature stress fibres restricted to the cell-substratum contact regions. These results suggest that the actin filaments elongate from the focal contacts and that structural rearrangement caused by phorbol esters is an energy-dependent phenomenon but is independent of de novo protein synthesis.
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Affiliation(s)
- M A Rahilly
- Department of Pathology, University Medical School, Edinburgh, U.K
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Tatsuta M, Iishi H, Nakaizumi A, Okuda S, Taniguchi H, Hiyama T, Tsukuma H, Oshima A. Fundal atrophic gastritis as a risk factor for gastric cancer. Int J Cancer 1993; 53:70-4. [PMID: 8416206 DOI: 10.1002/ijc.2910530114] [Citation(s) in RCA: 77] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
The role of atrophic gastritis of the gastric corpus (fundal atrophic gastritis) as a high-risk factor was investigated by studying operative findings and follow-up data on 690 patients with benign gastric diseases recorded at the Osaka Cancer Registry. The extent of fundal atrophic gastritis was determined by the endoscopic Congo red test. The patients were followed-up from the time of endoscopic examination (1968 to 1976) to December 31, 1987. The vital status of 654 patients (94.8%) at the end of the observation period was determined. During the follow-up period, 22 patients were found to have gastric cancer. The extent of fundal atrophic gastritis was shown to be closely related with the risk of developing gastric cancer. Patients who had been diagnosed as having severe fundal atrophic gastritis showed significantly higher risk of gastric cancer than patients who had been diagnosed as having little or no fundal atrophic gastritis (5.76-fold, calculated with adjustments for age, sex and the follow-up period). A positive linear relationship was found between the risk of developing gastric cancer and the extent of fundal atrophic gastritis. The observed number of gastric cancers was compared with the expected number calculated from the incidence in Osaka Prefecture. Analysis of the results showed that the observed and expected numbers of gastric cancers in patients with severe fundal atrophic gastritis were 11 and 4.8, respectively, the ratio of observed to expected numbers being 2.3 (p < 0.05). These findings indicate that severe fundal atrophic gastritis is a major risk factor for gastric cancer.
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Affiliation(s)
- M Tatsuta
- Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan
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Cornish JA, Kloc M, Decker GL, Reddy BA, Etkin LD. Xlcaax-1 is localized to the basolateral membrane of kidney tubule and other polarized epithelia during Xenopus development. Dev Biol 1992; 150:108-20. [PMID: 1537427 DOI: 10.1016/0012-1606(92)90011-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Xlcaax-1 is a novel, maternally expressed, 110-kDa, CAAX box containing protein that undergoes isoprenylation and palmitoylation through which it associates with the plasma membrane. We report here the cellular and subcellular localization of the xlcaax-1 protein during development of Xenopus laevis. Whole-mount immunocytochemistry and immunoperoxidase staining of tissue sections show that during development the xlcaax-1 protein accumulation is coincident with the differentiation of the epidermis, pronephros, and mesonephros. In the pronephros and mesonephros the xlcaax-1 protein is localized to the basolateral membrane of differentiated tubule epithelial cells. Thus, the xlcaax-1 protein serves as a marker for tubule formation and polarization during Xenopus kidney development. Xlcaax-1 may also be used as a marker for the functional differentiation of the epidermis and the epidermally derived portions of the lens and some cranial nerves. Western blot analysis shows that in the adult the xlcaax-1 protein is most abundant in kidney. Immunogold EM analysis shows that the xlcaax-1 protein is highly enriched in the basal infoldings of the basolateral membrane of the epithelial cells in adult kidney distal tubules. In addition, immunoperoxidase staining of tissue sections detected low levels of xlcaax-1 protein in the epithelial cells of skin, urinary bladder, gall bladder, and parietal glands of the stomach. The localization pattern of xlcaax-1 suggests that the protein may function in association with an ion transport channel or pump.
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Affiliation(s)
- J A Cornish
- Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston 77030
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Abstract
The association between achlorhydria and gastric carcinogenesis can be explained by a simple hypothesis based on the known cytological properties of neoplastic cells and the physiology of the stomach. Normal gastric secretions might ensure the rapid elimination of carcinomatous cells. Achlorhydria could be an important permissive factor in the development of gastric carcinoma.
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Affiliation(s)
- J P Seery
- Department of Clinical Pharmacology, Royal Infirmary of Edinburgh, UK
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