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1
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Chantarasrivong C, Higuchi Y, Tsuda M, Yamane Y, Hashida M, Konishi M, Komura N, Ando H, Yamashita F. Sialyl LewisX mimic-decorated liposomes for anti-angiogenic everolimus delivery to E-selectin expressing endothelial cells. RSC Adv 2019; 9:20518-20527. [PMID: 35515515 PMCID: PMC9065773 DOI: 10.1039/c9ra01943j] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 06/25/2019] [Indexed: 12/18/2022] Open
Abstract
In this study, we developed novel E-selectin-targeting liposomes, i.e., 3′-(1-carboxy)ethyl sialyl LewisX (3′-CE sLeX) mimic liposomes, for targeted delivery of everolimus (EVE) in anti-angiogenic therapy. We investigated the uptake and efficacy of these E-selectin targeting liposomes in inflammatory cytokine-treated human umbilical vein endothelial cells (HUVECs). The uptake of EVE in 3′-CE sLeX mimic liposomes increased steadily and almost caught up with the uptake of plain EVE at 3 h, which was higher than that in PEGylated liposomes (PEG-liposomes). Inhibition of uptake by anti-E-selectin antibody suggested involvement of E-selectin-mediated endocytotic processes. Migration in cells treated with EVE/3′-CE sLeX mimic liposomes was suppressed by more than half when compared to the control. This treatment was also seen to significantly inhibit the formation of capillary tubes and networks. In addition, Thr389 phosphorylation of pS6 kinase, as a marker of mTOR activity, was remarkably suppressed to less than endogenous levels by EVE/3′-CE sLeX mimic liposomes. In conclusion, the present study demonstrated that EVE/3′-CE sLeX mimic liposomes were intracellularly taken up by E-selectin and prompted anti-angiogenic effects of EVE involved in the mTOR signaling pathway. However, moderate retention of EVE in the liposomes might limit the targeting ability of 3′-CE sLeX mimic liposomes. Novel E-selectin-targeting liposomes deliver everolimus to E-selectin expressing endothelial cells and accelerate its anti-angiogenic effect.![]()
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Affiliation(s)
| | - Yuriko Higuchi
- Graduate School of Pharmaceutical Sciences
- Kyoto University
- Kyoto 606-8501
- Japan
| | - Masahiro Tsuda
- Graduate School of Pharmaceutical Sciences
- Kyoto University
- Kyoto 606-8501
- Japan
| | - Yuuki Yamane
- Graduate School of Pharmaceutical Sciences
- Kyoto University
- Kyoto 606-8501
- Japan
| | - Mitsuru Hashida
- Institute for Advanced Study
- Kyoto University
- Kyoto 606-8501
- Japan
| | - Miku Konishi
- Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN)
- Gifu University
- Gifu 501-1193
- Japan
| | - Naoko Komura
- Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN)
- Gifu University
- Gifu 501-1193
- Japan
| | - Hiromune Ando
- Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN)
- Gifu University
- Gifu 501-1193
- Japan
| | - Fumiyoshi Yamashita
- Graduate School of Pharmaceutical Sciences
- Kyoto University
- Kyoto 606-8501
- Japan
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2
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Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G, Psaila B, Kaplan RN, Bromberg JF, Kang Y, Bissell MJ, Cox TR, Giaccia AJ, Erler JT, Hiratsuka S, Ghajar CM, Lyden D. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer 2017; 17:302-317. [PMID: 28303905 DOI: 10.1038/nrc.2017.6] [Citation(s) in RCA: 1283] [Impact Index Per Article: 160.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.
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Affiliation(s)
- Héctor Peinado
- Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA
- Microenvironment and Metastasis Group, Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain
| | - Haiying Zhang
- Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA
| | - Irina R Matei
- Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA
| | - Bruno Costa-Silva
- Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA
- Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Avenida Brasília, Doca de Pedrouços, 1400-038 Lisbon, Portugal
| | - Ayuko Hoshino
- Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA
| | - Goncalo Rodrigues
- Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA
- Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, 4099-003 Porto, Portugal
| | - Bethan Psaila
- Centre for Haematology, Department of Medicine, Hammersmith Hospital, Imperial College London, London W12 0HS, UK
| | - Rosandra N Kaplan
- Center for Cancer Research, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10-Hatfield CRC, Room 1-3940, Bethesda, Maryland 20892, USA
| | - Jacqueline F Bromberg
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
| | - Yibin Kang
- Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA
| | - Mina J Bissell
- Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
| | - Thomas R Cox
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
| | - Amato J Giaccia
- Department of Radiation Oncology, Stanford University, Stanford, California 94305, USA
| | - Janine T Erler
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen 2200, Denmark
| | - Sachie Hiratsuka
- Department of Pharmacology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Tokyo 162-8666, Japan
| | - Cyrus M Ghajar
- Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
| | - David Lyden
- Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, New York 10021, USA
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
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3
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Chantarasrivong C, Ueki A, Ohyama R, Unga J, Nakamura S, Nakanishi I, Higuchi Y, Kawakami S, Ando H, Imamura A, Ishida H, Yamashita F, Kiso M, Hashida M. Synthesis and Functional Characterization of Novel Sialyl LewisX Mimic-Decorated Liposomes for E-selectin-Mediated Targeting to Inflamed Endothelial Cells. Mol Pharm 2017; 14:1528-1537. [DOI: 10.1021/acs.molpharmaceut.6b00982] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Chanikarn Chantarasrivong
- Department of Drug Delivery Research, Graduate School of Pharmaceutical
Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8302, Japan
| | - Akiharu Ueki
- Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan
- Institute for Integrated
Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshidaushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan
| | - Ryutaro Ohyama
- Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan
| | - Johan Unga
- Department of Drug Delivery Research, Graduate School of Pharmaceutical
Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8302, Japan
| | - Shinya Nakamura
- Department of Pharmaceutical Sciences,
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae,
Higashi-Osaka, Osaka 577-8502, Japan
| | - Isao Nakanishi
- Department of Pharmaceutical Sciences,
Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae,
Higashi-Osaka, Osaka 577-8502, Japan
| | - Yuriko Higuchi
- Department of Drug Delivery Research, Graduate School of Pharmaceutical
Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8302, Japan
| | - Shigeru Kawakami
- Department of Drug Delivery Research, Graduate School of Pharmaceutical
Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8302, Japan
| | - Hiromune Ando
- Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan
- Institute for Integrated
Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshidaushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan
- Gifu Center for Highly Advanced Integration
of Nano and Life Sciences (G-CHAIN), Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan
| | - Akihiro Imamura
- Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan
| | - Hideharu Ishida
- Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan
- Gifu Center for Highly Advanced Integration
of Nano and Life Sciences (G-CHAIN), Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan
| | - Fumiyoshi Yamashita
- Department of Drug Delivery Research, Graduate School of Pharmaceutical
Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8302, Japan
| | - Makoto Kiso
- Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan
- Institute for Integrated
Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshidaushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan
| | - Mitsuru Hashida
- Department of Drug Delivery Research, Graduate School of Pharmaceutical
Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8302, Japan
- Institute for Integrated
Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshidaushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan
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Giakoustidis A, Mudan S, Hagemann T. Tumour Microenvironment: Overview with an Emphasis on the Colorectal Liver Metastasis Pathway. CANCER MICROENVIRONMENT 2014; 8:177-86. [PMID: 25277516 DOI: 10.1007/s12307-014-0155-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Accepted: 09/21/2014] [Indexed: 12/31/2022]
Abstract
The tumour microenvironment (TME) represents a dynamic network that plays an important role in tumour initiation, proliferation, growth, and metastasis. Cell behaviour may be regulated by interplay of molecular interactions involving positive and negative reinforcement as well as a high level of cross-talk, which determines this system. Additionally, cancer involves cell proliferation, its malignancy defined by the tumour's ability to break down normal tissue architecture and by a dynamic process of invasion and metastasis. The metastatic cascade is regulated by a chain of molecular steps which triggers the progression of the developing cancer cell in the primary tumour into a number of transformations, leading to invasion and proceeding to metastases. Tumour-associated macrophages (TAMs) play a key-role in the progression from inflammatory conditions to cancer; TAMs are also capable of infiltrating the tumour microenvironment. Furthermore, myeloid-derived suppressor cells (MDSCs), a population of inhibitory immune cells, have been reported to increase in various cancer types, although characterising human MDSCs remains difficult, as their phenotype is quite variable. The future of cancer treatment is likely to involve creating more drugs that target these elements as well as others. An overview of the tumour's microenvironment is, therefore, presented in this paper, focusing on the metastatic pathways of primary colorectal cancer to the liver.
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Affiliation(s)
- Alexandros Giakoustidis
- Barts Cancer Institute, Queen Mary School of Medicine and Dentistry, University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK. .,The London Clinic, 116 Harley Street, London, W1G 7JL, UK.
| | - Satvinder Mudan
- Academic Department of Surgery, The Royal Marsden NHS Trust, Fulham Road, London, SW3 6JJ, UK.,Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W2 1PG, UK
| | - Thorsten Hagemann
- Barts Cancer Institute, Queen Mary School of Medicine and Dentistry, University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK
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Paschos KA, Majeed AW, Bird NC. Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance. World J Gastroenterol 2014; 20:3719-3737. [PMID: 24744570 PMCID: PMC3983432 DOI: 10.3748/wjg.v20.i14.3719] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 11/12/2013] [Accepted: 01/06/2014] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.
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6
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Kim SK, Moon WK, Park JY, Jung H. Inflammatory mimetic microfluidic chip by immobilization of cell adhesion molecules for T cell adhesion. Analyst 2012; 137:4062-8. [DOI: 10.1039/c2an35424a] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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7
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David A. Carbohydrate-based Biomedical Copolymers for Targeted Delivery of Anticancer Drugs. Isr J Chem 2010. [DOI: 10.1002/ijch.201000021] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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8
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Shamay Y, Paulin D, Ashkenasy G, David A. Multivalent Display of Quinic Acid Based Ligands for Targeting E-Selectin Expressing Cells. J Med Chem 2009; 52:5906-15. [DOI: 10.1021/jm900308r] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Yosi Shamay
- Department of Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel
| | - Denise Paulin
- Université Pierre et Marie Curie, Case Courrier 256, 7 Quai St. Bernard, 75252 Paris Cedex 5, France
| | - Gonen Ashkenasy
- Department of Chemistry, Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel
| | - Ayelet David
- Department of Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel
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9
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Aychek T, Miller K, Sagi-Assif O, Levy-Nissenbaum O, Israeli-Amit M, Pasmanik-Chor M, Jacob-Hirsch J, Amariglio N, Rechavi G, Witz IP. E-selectin regulates gene expression in metastatic colorectal carcinoma cells and enhances HMGB1 release. Int J Cancer 2008; 123:1741-50. [DOI: 10.1002/ijc.23375] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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10
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Gout S, Huot J. Role of cancer microenvironment in metastasis: focus on colon cancer. CANCER MICROENVIRONMENT 2008; 1:69-83. [PMID: 19308686 PMCID: PMC2654352 DOI: 10.1007/s12307-008-0007-2] [Citation(s) in RCA: 137] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2007] [Accepted: 02/13/2008] [Indexed: 12/13/2022]
Abstract
One person on three will receive a diagnostic of cancer during his life. About one third of them will die of the disease. In most cases, death will result from the formation of distal secondary sites called metastases. Several events that lead to cancer are under genetic control. In particular, cancer initiation is tightly associated with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations lead to unrestrained growth of the primary neoplasm and a propensity to detach and to progress through the subsequent steps of metastatic dissemination. This process depends tightly on the surrounding microenvironment. In fact, several studies support the point that tumour development relies on a continuous cross-talk between cancer cells and their cellular and extracellular microenvironments. This signaling cross-talk is mediated by transmembrane receptors expressed on cancer cells and stromal cells. The aim of this manuscript is to review how the cancer microenvironment influences the journey of a metastatic cell taking liver invasion by colorectal cancer cells as a model.
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Affiliation(s)
- Stéphanie Gout
- Le Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, 9 rue McMahon, Quebec, Canada
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11
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Gout S, Tremblay PL, Huot J. Selectins and selectin ligands in extravasation of cancer cells and organ selectivity of metastasis. Clin Exp Metastasis 2007; 25:335-44. [PMID: 17891461 DOI: 10.1007/s10585-007-9096-4] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2007] [Accepted: 08/30/2007] [Indexed: 01/09/2023]
Abstract
Metastatic spreading is a dreadful complication of neoplastic diseases that is responsible for most deaths due to cancer. It consists in the formation of secondary neoplasms from cancer cells that have detached from the primary site. The formation of these secondary sites is not random and several clinical observations indicate that the metastatic colonization exhibits organ selectivity. This organ tropism relies mostly on the complementary adhesive interactions between the cancer cells and their microenvironment. In particular, several lines of evidence suggest that the organ selectivity of colon cancer cells for the liver involves the binding of the circulating cancer cells to endothelial E-selectin. The aim of this review is to make an integrative up-date of the mechanisms that govern the organ selectivity of the metastatic process focusing more especially on the role of selectins and selectin ligands.
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Affiliation(s)
- Stéphanie Gout
- Le Centre de Recherche en Cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Quebec, Canada.
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D'Amico TA, Brooks KR, Joshi MBM, Conlon D, Herndon J, Petersen RP, Harpole DH. Serum Protein Expression Predicts Recurrence in Patients With Early-Stage Lung Cancer After Resection. Ann Thorac Surg 2006; 81:1982-7; discussion 1987. [PMID: 16731117 DOI: 10.1016/j.athoracsur.2006.01.042] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2003] [Revised: 01/05/2006] [Accepted: 01/09/2006] [Indexed: 11/20/2022]
Abstract
BACKGROUND Patients with early stage nonsmall-cell lung cancer who have undergone complete resection have a recurrence rate of approximately 50%, predominately due to the development of systemic metastases. This study is a prospective analysis of the expression of seven serum protein markers of invasion and metastasis, collected preoperatively (baseline) and serially after resection, to determine the relationship between marker expression and recurrence. METHODS Serum was collected from 196 patients with clinical stage I nonsmall-cell lung cancer who underwent resection over a 5-year period (1996 to 2000). Samples were drawn before resection and 1, 4, 6, 12, 18, and 24 months postoperatively. All patients were followed for at least 24 months or until death. Serum protein levels of vascular endothelial growth factor, hepatocyte growth factor), E-selectin, CD44, basic fibroblast growth factor, urokinase plasminogen activator, and urokinase plasminogen activator receptor were determined using enzyme-linked immunosorbent assay. RESULTS To date, 73 patients (37%) have demonstrated recurrence. Baseline levels of only 1 marker (CD44) correlated with pathologic stage (p = 0.02). Analysis of the serial samples demonstrated that recurrence was predicted (before clinical or radiographic determination) by decreasing levels of E-selectin (p = 0.002), increasing levels of CD44 (p = 0.001), and increasing levels of urokinase plasminogen activator receptor (p = 0.03). CONCLUSIONS This study demonstrates the potential to predict recurrence after resection in patients with early-stage nonsmall-cell lung cancer using a panel of serum protein markers. Early identification of patients with recurrence may improve the efficacy of systemic therapy.
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MESH Headings
- Adenocarcinoma/blood
- Adenocarcinoma/pathology
- Adenocarcinoma/secondary
- Adenocarcinoma/surgery
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor/blood
- Carcinoma, Non-Small-Cell Lung/blood
- Carcinoma, Non-Small-Cell Lung/pathology
- Carcinoma, Non-Small-Cell Lung/secondary
- Carcinoma, Non-Small-Cell Lung/surgery
- Carcinoma, Squamous Cell/blood
- Carcinoma, Squamous Cell/pathology
- Carcinoma, Squamous Cell/secondary
- Carcinoma, Squamous Cell/surgery
- E-Selectin/blood
- Enzyme-Linked Immunosorbent Assay
- Female
- Fibroblast Growth Factor 2/blood
- Follow-Up Studies
- Hepatocyte Growth Factor/blood
- Humans
- Hyaluronan Receptors/blood
- Life Tables
- Lung Neoplasms/blood
- Lung Neoplasms/pathology
- Lung Neoplasms/surgery
- Male
- Middle Aged
- Neoplasm Proteins/blood
- Neoplasm Recurrence, Local/blood
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Staging
- Pneumonectomy
- Postoperative Period
- Predictive Value of Tests
- Receptors, Cell Surface/blood
- Receptors, Urokinase Plasminogen Activator
- Survival Analysis
- Urokinase-Type Plasminogen Activator/blood
- Vascular Endothelial Growth Factor A/blood
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Affiliation(s)
- Thomas A D'Amico
- Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
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Sheen-Chen SM, Eng HL, Huang CC, Chen WJ. Serum levels of soluble E-selectin in women with breast cancer. Br J Surg 2004; 91:1578-81. [PMID: 15386328 DOI: 10.1002/bjs.4513] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Abstract
Background
Increasing evidence suggests that E-selectin contributes to tumour growth and metastasis, possibly by increasing angiogenesis and the adhesion of tumour cells to endothelial cells at distant sites. This study aimed to examine the relationship between preoperative levels of circulating soluble E-selectin and breast cancer.
Methods
Sixty-four consecutive women undergoing surgery for invasive breast cancer were studied prospectively. Venous blood samples were collected before the operation. A control group consisted of 16 patients with a benign breast tumour (eight with fibrocystic disease and eight with fibroadenoma). Serum concentrations of soluble E-selectin were measured by the quantitative sandwich enzyme immunoassay technique and compared with clinicopathological information.
Results
The mean(s.d.) serum level of soluble E-selectin in patients with invasive breast cancer was 73·7(20·9) ng/ml, compared with 36·3(5·6) ng/ml in the control group (P < 0·001). Furthermore, the serum levels of soluble E-selectin were significantly higher in women with oestrogen receptor-negative tumours (P = 0·001), poorly differentiated tumours (P < 0·001), more advanced primary tumour stage (P < 0·001), involved lymph nodes (P < 0·001), distant metastases (P < 0·001) and more advanced tumour node metastasis (TNM) stage (P < 0·001). On multivariate analysis, TNM stage (P < 0·001) was found to be an independent factor with regard to higher serum levels of soluble E-selectin.
Conclusion
Preoperative serum levels of soluble E-selectin might reflect the severity of invasive breast cancer; further evaluation is warranted.
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Affiliation(s)
- S-M Sheen-Chen
- Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, College of Medicine, Chang Gung University, Taiwan, Republic of China.
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Abstract
The carbohydrate determinants, sialyl Lewis A and sialyl Lewis X, which are frequently expressed on human cancer cells, serve as ligands for a cell adhesion molecule of the selectin family, E-selectin, which is expressed on vascular endothelial cells. These carbohydrate determinants are involved in the adhesion of cancer cells to vascular endothelium and thus contribute to hematogenous metastasis of cancer. The initial adhesion mediated by these molecules triggers activation of integrin molecules through the action of several cytokines and leads to the extravasation of cancer cells. Cancer cells also produce humoral factors that facilitate E-selectin expression on endothelial cells. The degree of expression of the carbohydrate ligands at the surface of cancer cells is well correlated with the frequency of hematogenous metastasis and prognostic outcome of patients with cancers. The alteration of glycosyltransferase activities that leads to the enhanced expression of these carbohydrate ligands on cancer cell surface are currently being investigated.
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Affiliation(s)
- R Kannagi
- Molecular Pathology, Aichi Cancer Center, Nagoya, Japan
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