• antigen presentation
• cervical cancer
• immunosurveillance
• interferon‑induced transmembrane proteins
• invasion
• mass spectrometry
• membrane protein
• migration
• surfaceome

• Humans
• Uterine Cervical Neoplasms/pathology
• Uterine Cervical Neoplasms/genetics
• Uterine Cervical Neoplasms/metabolism
• Uterine Cervical Neoplasms/immunology
• Female
• Antigens, Differentiation/metabolism
• Antigens, Differentiation/genetics
• Membrane Proteins/metabolism
• Membrane Proteins/genetics
• Gene Expression Regulation, Neoplastic
• RNA-Binding Proteins/metabolism
• RNA-Binding Proteins/genetics
• Cell Movement
• Proteomics/methods
• Cell Line, Tumor
• Interferon-gamma/pharmacology
• Interferon-gamma/metabolism
• Cell Adhesion
• Phenotype
• Proteome

• ATF4
• BOK
• COPD
• airway homeostasis
• differentiated progeny cells
• influenza infection
• integrated stress response
• lung epithelial cells
• mitochondria
• progenitor basal cells

• Animals
• Mitochondria/metabolism
• Mice
• Cell Differentiation
• Mitochondrial Proteins/metabolism
• Stem Cells/metabolism
• Stem Cells/cytology
• ATP-Dependent Proteases/metabolism
• ATP-Dependent Proteases/genetics
• Pulmonary Disease, Chronic Obstructive/pathology
• Pulmonary Disease, Chronic Obstructive/metabolism
• Humans
• Cell Proliferation
• Mice, Inbred C57BL
• Apoptosis

• invasion
• migration
• non-coding RNA
• small peptide
• tumor

• Scientific Research Fund of Liaoning Provincial Education Department

• Cervical cancer
• Cervical epithelial neoplasia
• Correlation analysis
• E6/E7 mRNA
• Human papilloma change with virus

• Non-small cell lung cancer
• antibody-drug conjugates
• novel biomarkers
• precision oncology

• Diagnosis
• Drug resistance
• Pheochromocytoma (PCC)
• Prognosis
• miRNA

• Humans
• MicroRNAs
• Pheochromocytoma/diagnosis
• Pheochromocytoma/genetics
• Pheochromocytoma/pathology
• Adrenal Gland Neoplasms/diagnosis
• Adrenal Gland Neoplasms/genetics
• Adrenal Gland Neoplasms/pathology
• Prognosis
• Biomarkers, Tumor
• Gene Expression Regulation, Neoplastic

• CD166
• Gastric cancer
• Human epidermal growth factor receptor 2 (HER-2)
• Immunohistochemistry (IHC)
• Intestinal type
• Signet Ring Cell Carcinoma

• Humans
• Clinical Relevance
• Biomarkers, Tumor/metabolism
• Stomach Neoplasms/pathology
• Prospective Studies
• Prognosis
• Receptor, ErbB-2

• 16274 Iran University of Medical Sciences

• Cancer
• Cancer cell membrane
• Cancer research
• Extracellular vesicles
• Tumor cell lysate
• Tumor organoids

• RAGEs
• S100A8/A9
• TLR4
• cancer
• inflammation

• PCa
• cancer stem cells
• signaling pathway

• ALCAM
• CD166
• SRC kinase
• gastric cancer
• mesothelial cells
• pancreatic cancer
• peritoneal metastasis
• transcoelomic metastasis
• tumour-mesothelial interaction

• Humans
• Activated-Leukocyte Cell Adhesion Molecule/genetics
• Activated-Leukocyte Cell Adhesion Molecule/metabolism
• Cell Adhesion
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology
• src-Family Kinases/metabolism
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology
• Peritoneal Neoplasms/secondary

Human papillomavirus (HPV) oncogenes E6 and E7 are essential for HPV-related cancer development. Here, we developed a cell line model using lentiviruses for transfection of the HPV16 oncogenes E6 and E7 and investigated the differences in mRNA expression during cell adhesion and chemokine secretion. Subsequently, RNA sequencing (RNA-seq) analysis was performed to explore the differences in mRNA expression. Compared to levels in the control group, 2,905 differentially expressed mRNAs (1,261 downregulated and 1,644 upregulated) were identified in the HaCaT-HPV16E6E7 cell line. To predict the functions of these differentially expressed genes (DEGs) the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used. Protein–protein interactions were established, and the hub gene was identified based on this network. Real-time quantitative-PCR (RT-qPCR) was conducted to confirm the levels of 14 hub genes, which were consistent with the RNA-seq data. According to this, we found that these DEGs participate in the extracellular matrix (ECM), cell adhesion, immune control, and cancer-related signaling pathways. Currently, an increasing number of clinicians depend on E6/E7mRNA results to make a comprehensive judgment of cervical precancerous lesions. In this study, 14 hub genes closely related to the expression of cell adhesion ability and chemokines were analyzed in HPV16E6E7-stably expressing cell lines, which will open up new research ideas for targeting E6E7 in the treatment of HPV-related cancers.

• fibrosis
• hepatic stellate cells (HSCs)
• inflammation
• liver sinusoidal endothelial cells (LSECs)
• nonalcoholic steatohepatitis - NASH
• vascular cell adhesion molecule 1 (VCAM1)

Colorectal cancer (CRC) and ovarian cancer (OvC) patients frequently develop peritoneal metastasis, a condition associated with a very poor prognosis. In these cancers, tumor-derived extracellular vesicles (EVs) cause immunosuppression, facilitate the direct attachment and invasion of cancer cells through the mesothelium, induce the conversion of peritoneal mesothelial cells (PMCs) into cancer-associated fibroblasts (CAFs) and transfer a more aggressive phenotype amongst cancer cells. Although the promoting role of EVs in CRC and OvC peritoneal metastasis is well established, the specific molecules that mediate the interactions between tumor-derived EVs and immune and non-immune target cells remain elusive. Here, we employed the SKOV-3 (ovarian adenocarcinoma) and Colo-320 (colorectal adenocarcinoma) human cell lines as model systems to study the interactions and uptake of EVs produced by ovarian carcinoma and colorectal carcinoma cells, respectively. We established that the adhesion molecule ALCAM/CD166 is involved in the interaction of cancer-derived EVs with recipient cancer cells (a process termed “EV binding” or “EV docking”) and in their subsequent uptake by these cells. The identification of ALCAM/CD166 as a molecule mediating the docking and uptake of CRC and OvC-derived EVs may be potentially exploited to block the peritoneal metastasis cascade promoted by EVs in CRC and OvC patients.

• ALCAM
• CD166
• colorectal cancer
• docking
• extracellular vesicles
• intercellular communication
• ovarian cancer
• uptake

Chronic rhinosinusitis with polyps (CRSwNP) is characterized by high heterogeneity and postoperative recurrence rate. This study aimed to explore the clinical significance of activated leukocyte cell adhesion molecule (ALCAM) in endotyping CRSwNP and predicting its recurrence.

We recruited 120 CRSwNP patients including 70 non-eosinophilic CRSwNP (neCRSwNP) and 50 eosinophilic CRSwNP (eCRSwNP) patients, and 40 healthy controls (HCs). Serum and tissue samples were collected. Serum ALCAM levels were detected by enzyme-linked immunosorbent assay (ELISA), and tissue ALCAM expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC). The predictive values of ALCAM expression for CRSwNP endotypes and postoperative recurrence were assessed.

The serum levels of ALCAM were significantly increased in CRSwNP patients in comparison with HCs and were correlated with the peripheral eosinophil count, tissue eosinophil counts, and percentage. Multivariate analysis and receiver operating characteristic (ROC) curve highlighted that serum ALCAM levels were associated with CRSwNP endotypes. Tissue ALCAM expression was significantly enhanced in CRSwNP patients, especially in eCRSwNP patients. At the end of the study, 110 patients completed the follow-up schedule, 78 patients were categorized into the non-recurrent group, and the other 32 patients were included in the recurrent group. The serum ALCAM levels were elevated in the recurrent group compared with the non-recurrent group, and ALCAM expression in the tissue was significantly elevated. The ROC curve exhibited a high predictive ability of serum ALCAM in predicting postoperative recurrence. Logistic regression and Kaplan–Meier curves demonstrated that serum ALCAM was an independent risk factor for postoperative recurrence.

This is the first report suggesting that ALCAM expression was upregulated and associated with mucosal eosinophil infiltration and CRSwNP recurrence. Serum ALCAM could be a promising biomarker for distinguishing endotypes and predicting postoperative recurrence in CRwNP patients.

Drug-resistance is a major problem preventing a cure in patients with multiple myeloma (MM). Previously, we demonstrated that activated-leukocyte-cell-adhesion-molecule (ALCAM) is a prognostic factor in MM and inhibits EGF/EGFR-initiated MM clonogenicity. In this study, we further showed that the ALCAM-EGF/EGFR axis regulated the MM side population (SP)-mediated drug-resistance. ALCAM-knockdown MM cells displayed an enhanced ratio of SP cells in the presence of bone marrow stromal cells (BMSCs) or with the supplement of recombinant EGF. SP MM cells were resistant to chemotherapeutics melphalan or bortezomib. Drug treatment stimulated SP-genesis. Mechanistically, EGFR, primed with EGF, activated the hedgehog pathway and promoted the SP ratio; meanwhile, ALCAM inhibited EGFR downstream pro-MM cell signaling. Further, SP MM cells exhibited an increased number of mitochondria compared to the main population. Interference of the mitochondria function strongly inhibited SP-genesis. Animal studies showed that combination therapy with both an anti-MM agent and EGFR inhibitor gefitinib achieved prolonged MM-bearing mice survival. Hence, our work identifies ALCAM as a novel negative regulator of MM drug-resistance, and EGFR inhibitors may be used to improve MM therapeutic efficacy.

• Cancer
• Immunoconjugates
• Immunotherapy
• Monoclonal antibodies
• Tumor microenvironment

• ALCAM
• CD166
• Pancreatic cancer
• activated leukocyte cell adhesion molecule
• embolism
• metastasis
• progression
• survival
• tumour-endothelial interaction

• Activated-Leukocyte Cell Adhesion Molecule
• Antigens, CD
• Cell Adhesion Molecules, Neuronal
• ErbB Receptors/genetics
• Fetal Proteins
• Hedgehog Proteins
• Humans
• Phosphatidylinositol 3-Kinases
• Signal Transduction

ALCAM (activated leukocyte cell adhesion molecule) is an important regulator in human cancers, particularly solid tumours. Its expression in cancer tissues has prognostic values depending on cancer types and is also linked to distant metastases. A truncated form, soluble form of ALCAM (sALCAM) in circulation has been suggested to be a prognostic indicator and a potential therapeutic tool. This article summarises recent findings and progress in ALCAM and its involvement in cancer, with a primary focus on its clinical connections and therapeutic values.

Activated leukocyte cell adhesion molecule (ALCAM), also known as CD166, is a cell adhesion protein that is found in multiple cell types. ALCAM has multiple and diverse roles in various physiological and pathological conditions, including inflammation and cancer. There has been compelling evidence of ALCAM’s prognostic value in solid cancers, indicating that it is a potential therapeutic target. The present article overviews the recent findings and progress in ALCAM and its involvement in cancer, with a primary focus on its clinical connections in cancer and therapeutic values.

• ALCAM
• CD166
• activated leukocyte cell adhesion molecule
• cancer
• prognosis
• survival
• therapeutic targets

• ALCAM/CD166
• Cancer stem cell marker
• Shedding
• Structure
• Tumor progression

• Activated-Leukocyte Cell Adhesion Molecule
• Antigens, CD
• Biomarkers, Tumor
• Cell Adhesion
• Cell Adhesion Molecules, Neuronal
• Fetal Proteins
• Humans
• Neoplasms
• Neoplastic Stem Cells

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166⁺ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166⁺ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anti-cancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.

Cell adhesion molecules (CAMs) of the cadherin, integrin, immunoglobulin, and selectin protein families are indispensable for the formation and maintenance of multicellular tissues, especially epithelia. In the epidermis, they are involved in cell–cell contacts and in cellular interactions with the extracellular matrix (ECM), thereby contributing to the structural integrity and barrier formation of the skin. Bulk and single cell RNA sequencing data show that >170 CAMs are expressed in the healthy human skin, with high expression levels in melanocytes, keratinocytes, endothelial, and smooth muscle cells. Alterations in expression levels of CAMs are involved in melanoma propagation, interaction with the microenvironment, and metastasis. Recent mechanistic analyses together with protein and gene expression data provide a better picture of the role of CAMs in the context of skin physiology and melanoma. Here, we review progress in the field and discuss molecular mechanisms in light of gene expression profiles, including recent single cell RNA expression information. We highlight key adhesion molecules in melanoma, which can guide the identification of pathways and strategies for novel anti-melanoma therapies.

• GTEx consortium
• Human Protein Atlas
• cadherins
• integrins
• melanocytes
• selectins
• single cell RNA sequencing
• tumour microenvironment

• Cell Adhesion
• Cell Adhesion Molecules/metabolism
• Cell Communication
• Humans
• Melanocytes/cytology
• Melanocytes/metabolism
• Melanocytes/pathology
• Melanoma/metabolism
• Skin/cytology
• Skin/metabolism
• Skin/pathology
• Skin Neoplasms/metabolism
• Tumor Microenvironment

• advanced maternal age
• placenta
• senescence
• trophoblast
• α-klotho

• Animals
• Female
• Humans
• Klotho Proteins/metabolism
• Maternal Age
• Mice
• Placenta/abnormalities
• Pregnancy
• Trophoblasts/pathology

• National Natural Science Foundation of China
• Chongqing Science and Technology Commission

The most distal portion of the ventricular conduction system (VCS) contains cardiac Purkinje cells (PCs), which are essential for synchronous activation of the ventricular myocardium. Contactin-2 (CNTN2), a member of the immunoglobulin superfamily of cell adhesion molecules (IgSF-CAMs), was previously identified as a marker of the VCS. Through differential transcriptional profiling, we discovered two additional highly enriched IgSF-CAMs in the VCS: NCAM-1 and ALCAM. Immunofluorescence staining showed dynamic expression patterns for each IgSF-CAM during embryonic and early postnatal stages, but ultimately all three proteins became highly enriched in mature PCs. Mice deficient in NCAM-1, but not CNTN2 or ALCAM, exhibited defects in PC gene expression and VCS patterning, as well as cardiac conduction disease. Moreover, using ST8sia2 and ST8sia4 knockout mice, we show that inhibition of post-translational modification of NCAM-1 by polysialic acid leads to disrupted trafficking of sarcolemmal intercalated disc proteins to junctional membranes and abnormal expansion of the extracellular space between apposing PCs. Taken together, our data provide insights into the complex developmental biology of the ventricular conduction system.

Summary: The cell adhesion molecule NCAM-1 and its post-translational modification by polysialylation are required for normal formation and function of the specialized ventricular conduction system.

• Cardiac conduction system
• Cell adhesion molecule
• Mouse
• NCAM-1
• Polysialic acid
• Purkinje cell
• Ventricular conduction system

Brain metastasis (BM) in non-small-cell lung cancer (NSCLC) has a very poor prognosis. Recent studies have demonstrated the importance of cell adhesion molecules in tumor metastasis. The aim of our study was to investigate the role of activated leukocyte cell adhesion molecule (ALCAM) in BM formation in NSCLC.

Immunohistochemical analysis was performed on 143 NSCLC primary tumors and BM. A correlation between clinicopathological parameters and survival was developed. Biological properties of ALCAM were assessed in vitro by gene ablation using CRISPR/Cas9 technology in the NCI-H460 NSCLC cell line and in vivo by intracranial and intracardial cell injection of NCI-H460 cells in NMRI-Foxn1^nu/nu mice.

ALCAM expression was significantly upregulated in NSCLC brain metastasis (P = 0.023) with a de novo expression of ALCAM in 31.2% of BM. Moderate/strong ALCAM expression in both primary NSCLC and brain metastasis was associated with shortened survival. Functional analysis of an ALCAM knock-out (KO) cell line showed a significantly decreased cell adhesion capacity to human brain endothelial cells by 38% (P = 0.045). In vivo studies showed significantly lower tumor cell dissemination in mice injected with ALCAM-KO cells in both mouse models, and both the number and size of BM were significantly diminished in ALCAM depleted tumors.

Our findings suggest that elevated levels of ALCAM expression promote BM formation in NSCLC through increased tumor cell dissemination and interaction with the brain endothelial cells. Therefore, ALCAM could be targeted to reduce the occurrence of BM.

1. ALCAM expression associates with poor prognosis and brain metastasis in NSCLC.

2. ALCAM mediates interaction of NSCLC tumor cells with brain vascular endothelium.

3. ALCAM might represent a novel preventive target to reduce the occurrence of BM in NSCLC.

• ALCAM adhesion
• NSCLC brain metastasis
• blood-brain barrier

CD6 is a lymphocyte surface co-receptor physically associated with the T-cell receptor (TCR)/CD3 complex at the center of the immunological synapse. There, CD6 assists in cell-to-cell contact stabilization and modulation of activation/differentiation events through interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), its main reported ligand. While accumulating evidence is attracting new interest on targeting CD6 for therapeutic purposes in autoimmune disorders, little is known on its potential in cancer. In an attempt to elucidate the in vivo relevance of blocking CD6-mediated interactions in health and disease, we explored the consequences of expressing high circulating levels of a soluble form CD6 (sCD6) as a decoy receptor.

High sCD6 serum levels were achieved by using transgenic C57BL/6 mice expressing human sCD6 under the control of lymphoid-specific transcriptional elements (shCD6LckEμTg) or wild type either transduced with hepatotropic adeno-associated virus coding for mouse sCD6 or undergoing repeated infusions of recombinant human sCD6 protein. Characterization of sCD6-induced changes was performed by ex vivo flow cytometry and functional analyses of mouse lymphoid organ cells. The in vivo relevance of those changes was explored by challenging mice with subcutaneous or metastatic tumors induced by syngeneic cancer cells of different lineage origins.

Through a combination of in vitro and in vivo studies, we show that circulating sCD6 expression induces defective regulatory T cell (Treg) generation and function, decreased CD166/ALCAM-mediated tumor cell proliferation/migration and impaired galectin-induced T-cell apoptosis, supporting the fact that sCD6 modulates antitumor lymphocyte effector function and tumorigenesis. Accordingly, sCD6 expression in vivo resulted in delayed subcutaneous tumor growth and/or reduced metastasis on challenge of mice with syngeneic cancer cells.

Evidence is provided for the disruption of CD6 receptor–ligand interactions as a feasible immunomodulatory approach in cancer.

• immunology
• oncology

• Activated leukocyte cell adhesion molecule
• Allergic rhinitis
• Biomarker
• Sublingual immunotherapy

• Angiogenesis
• Endometrial mesenchymal stem cells
• Endometriosis
• Endometriotic mesenchymal stem cells
• Immunomodulation

• (q)PCR, (quantitative) polymerase chain reaction
• AD, adipose
• AF, Amniotic Fluid
• ALCAM, Activated-Leukocyte Cell Adhesion Molecule
• Activated-leukocyte cell adhesion molecule
• BM, bone marrow
• BSG, Basigin
• Biomarker
• CD, cluster of differentiation
• CLIC1, chloride intracellular channel 1
• CLIC4, chloride intracellular channel 4
• Cq, Quantification cycle
• DF, Dermal Fibroblasts
• DP, Dental Pulp
• EDIL3, EGF like repeats and discoidin domains 3
• ENG, Endoglin
• EPHA2, EPH receptor A2
• ER, Endoplasmatic Reticulum
• FACS, Fluorescence Assisted Cell Sorting
• FN1, Fibronectin 1
• IGFBP7, insulin like growth factor binding protein 7
• ISCT, International Society for Cell and Gene Therapy
• ITGA1, integrin subunit alpha 1
• LAMP1, lysosomal associated membrane protein 1
• LRRC59, leucine rich repeat containing 59
• MCAM, melanoma cell adhesion molecule
• MM, Multiple Myeloma
• MPC, Mesenchymal Progenitor Cell
• MSC
• MSC, Mesenchymal Stromal Cells
• NECTIN2, nectin cell adhesion molecule 2
• NK, Natural Killer
• NT5E, 5′-nucleotidase ecto
• OS, Osteosarcoma
• PL, Placenta
• PPIA, peptidylprolyl isomerase A
• PUM1, pumilio RNA binding family member 1
• RM, Regenerative Medicine
• RNA
• RNA-seq, RNA sequencing
• RT, Reverse Transcriptase
• Regenerative medicine
• SEM, Standard Error of the Mean
• TBP, TATA-box binding protein
• TCF, Tissue Culture Plate
• TE, Tissue Engineering
• TFRC, transferrin receptor
• THY1, Thy-1 cell surface antigen
• TLN1, Talin 1
• TMEM47, transmembrane protein 47
• UC, umbilical cord
• YWHAZ, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta
• cDNA, DNA complementary to RNA
• qPCR