The Role of Immunoglobulin Superfamily Cell Adhesion Molecules in Cancer Metastasis

Metastasis is a major clinical problem and results in a poor prognosis for most cancers. The metastatic pathway describes the process by which cancer cells give rise to a metastatic lesion in a new tissue or organ. It consists of interconnecting steps all of which must be successfully completed to result in a metastasis. Cell-cell adhesion is a key aspect of many of these steps. Adhesion molecules belonging to the immunoglobulin superfamily (Ig-SF) commonly play a central role in cell-cell adhesion, and a number of these molecules have been associated with cancer progression and a metastatic phenotype. Surprisingly, the contribution of Ig-SF members to metastasis has not received the attention afforded other cell adhesion molecules (CAMs) such as the integrins. Here we examine the steps in the metastatic pathway focusing on how the Ig-SF members, melanoma cell adhesion molecule (MCAM), L1CAM, neural CAM (NCAM), leukocyte CAM (ALCAM), intercellular CAM-1 (ICAM-1) and platelet endothelial CAM-1 (PECAM-1) could play a role. Although much remains to be understood, this review aims to raise the profile of Ig-SF members in metastasis formation and prompt further research that could lead to useful clinical outcomes.

[1]  J. Pollard,et al.  Microenvironmental regulation of metastasis , 2009, Nature Reviews Cancer.

[2]  I. Fidler,et al.  Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. , 2007, Endocrine reviews.

[3]  Yuan Liu,et al.  Enforced expression of METCAM/MUC18 increases tumorigenesis of human prostate cancer LNCaP cells in nude mice. , 2011, The Journal of urology.

[4]  Judith P. Johnson Cell Adhesion Molecules in the Development and Progression of Malignant Melanoma , 2004, Cancer and Metastasis Reviews.

[5]  T. Camenisch,et al.  Elevated glucose inhibits VEGF-A–mediated endocardial cushion formation , 2003, The Journal of cell biology.

[6]  R. Lotan,et al.  Carcinoembryonic antigen and other glycoconjugates act as ligands for galectin-3 in human colon carcinoma cells. , 1995, Cancer research.

[7]  Shin Ishii,et al.  Collective Cell Migration , 2013 .

[8]  Rakesh K Jain,et al.  Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed? , 2007, The Lancet. Oncology.

[9]  Suyun Huang,et al.  Fully human antibodies to MCAM/MUC18 inhibit tumor growth and metastasis of human melanoma. , 2002, Cancer research.

[10]  P. Willems,et al.  Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD), a novel actor in invasive growth, controls matrix metalloproteinase activity. , 2005, Cancer research.

[11]  F. Bertucci,et al.  CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines , 2009, Breast Cancer Research.

[12]  G. Botti,et al.  Human Melanoma Metastases Express Functional CXCR4 , 2006, Clinical Cancer Research.

[13]  Michael Karin,et al.  NF-κB in cancer: from innocent bystander to major culprit , 2002, Nature Reviews Cancer.

[14]  C. Roland,et al.  ICAM-1 expression determines malignant potential of cancer. , 2007, Surgery.

[15]  Ajit Varki,et al.  Molecular basis of metastasis. , 2009, The New England journal of medicine.

[16]  Mark W Dewhirst,et al.  Intravascular location of breast cancer cells after spontaneous metastasis to the lung. , 2002, The American journal of pathology.

[17]  H. Gabius,et al.  Phosphorylation of adhesion- and growth-regulatory human galectin-3 leads to the induction of axonal branching by local membrane L1 and ERM redistribution , 2010, Journal of Cell Science.

[18]  N. Koshikawa,et al.  Matrilysin (MMP-7) induces homotypic adhesion of human colon cancer cells and enhances their metastatic potential in nude mouse model , 2003, Oncogene.

[19]  S Etienne-Manneville,et al.  Polarity proteins in migration and invasion , 2008, Oncogene.

[20]  C. Streuli,et al.  Adhesion-Mediated Signaling in the Regulation of Mammary Epithelial Cell Survival , 1999, Journal of Mammary Gland Biology and Neoplasia.

[21]  P. Friedl,et al.  Tumour-cell invasion and migration: diversity and escape mechanisms , 2003, Nature Reviews Cancer.

[22]  M. Herlyn,et al.  Reciprocal regulation of MelCAM and AKT in human melanoma , 2003, Oncogene.

[23]  N. Longo,et al.  Stromal Cell-Derived Factor-1α Promotes Melanoma Cell Invasion across Basement Membranes Involving Stimulation of Membrane-Type 1 Matrix Metalloproteinase and Rho GTPase Activities , 2004, Cancer Research.

[24]  H. Hua,et al.  Matrix metalloproteinases in tumorigenesis: an evolving paradigm , 2011, Cellular and Molecular Life Sciences.

[25]  Jie Zhou,et al.  Akt1 governs breast cancer progression in vivo , 2007, Proceedings of the National Academy of Sciences.

[26]  Q. Zeng,et al.  Neural cell adhesion molecule potentiates invasion and metastasis of melanoma cells through CAMP-dependent protein kinase and phosphatidylinositol 3-kinase pathways. , 2011, The international journal of biochemistry & cell biology.

[27]  Hyung Jin Kim,et al.  Vascular Endothelial Growth Factor Expression of Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and E-selectin through Nuclear Factor-κB Activation in Endothelial Cells* , 2001, The Journal of Biological Chemistry.

[28]  J. Massagué,et al.  Cancer Metastasis: Building a Framework , 2006, Cell.

[29]  É. Vivier,et al.  Outside-in Signaling Pathway Linked to CD146 Engagement in Human Endothelial Cells* , 2001, The Journal of Biological Chemistry.

[30]  H. Nakshatri,et al.  NF-κ B Promotes Breast Cancer Cell Migration and Metastasis by Inducing the Expression of the Chemokine Receptor CXCR4* , 2003, Journal of Biological Chemistry.

[31]  F. Balkwill The significance of cancer cell expression of the chemokine receptor CXCR4. , 2004, Seminars in cancer biology.

[32]  Erik Sahai,et al.  Illuminating the metastatic process , 2007, Nature Reviews Cancer.

[33]  L. Puricelli,et al.  The neural cell adhesion molecule is involved in the metastatic capacity in a murine model of lung cancer , 2010, Molecular carcinogenesis.

[34]  Georg Krupitza,et al.  Initial steps of metastasis: Cell invasion and endothelial transmigration , 2011, Mutation research.

[35]  Ø. Rekdal,et al.  Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells , 2011, BMC Cancer.

[36]  R. Moon,et al.  Wnt5a Control of Cell Polarity and Directional Movement by Polarized Redistribution of Adhesion Receptors , 2008, Science.

[37]  A. Puisieux,et al.  Metastasis: a question of life or death , 2006, Nature Reviews Cancer.

[38]  F. Poulsen,et al.  Structural Biology of NCAM , 2008, Neurochemical Research.

[39]  A. M. Wu,et al.  Human galectin-3 (Mac-2 antigen): defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region. , 2011, Biochimica et biophysica acta.

[40]  J. Madri,et al.  Platelet-endothelial cell adhesion molecule-1 modulates endothelial migration through its immunoreceptor tyrosine-based inhibitory motif. , 2003, Biochemical and biophysical research communications.

[41]  M. Bar‐eli,et al.  Dominant-negative CREB inhibits tumor growth and metastasis of human melanoma cells , 1997, Oncogene.

[42]  J. Johnson,et al.  Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. , 1997, Cancer research.

[43]  Neha S. Gandhi,et al.  Platelet endothelial cell adhesion molecule 1 (PECAM-1) and its interactions with glycosaminoglycans: 2. Biochemical analyses. , 2008, Biochemistry.

[44]  G. Semenza Targeting HIF-1 for cancer therapy , 2003, Nature Reviews Cancer.

[45]  M Dietel,et al.  ALCAM/CD166 is overexpressed in colorectal carcinoma and correlates with shortened patient survival , 2004, Journal of Clinical Pathology.

[46]  Julia M. Lewis,et al.  Regulation of Cutaneous Malignancy by γδ T Cells , 2001, Science.

[47]  R L Juliano,et al.  Signal transduction by cell adhesion receptors and the cytoskeleton: functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members. , 2002, Annual review of pharmacology and toxicology.

[48]  Lena Claesson-Welsh,et al.  Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. , 2006, Experimental cell research.

[49]  Hong Yang,et al.  Angiogenic effect of intercellular adhesion molecule-1 , 2007, Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban.

[50]  A. Ben-Ze'ev,et al.  L1-CAM in cancerous tissues. , 2008, Expert opinion on biological therapy.

[51]  G. Stamatoyannopoulos,et al.  Down-regulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro. , 2003, Cancer research.

[52]  D. Bullard,et al.  Intercellular Adhesion Molecule-1 (ICAM-1) Regulates Endothelial Cell Motility through a Nitric Oxide-dependent Pathway* , 2004, Journal of Biological Chemistry.

[53]  Peiyu Li,et al.  A novel anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis and tumor growth. , 2003, Blood.

[54]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[55]  S. Hwang,et al.  Chemokines, chemokine receptors, and cancer metastasis , 2006, Journal of leukocyte biology.

[56]  P. Altevogt,et al.  L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells. , 2007, Gynecologic oncology.

[57]  Erkki Ruoslahti,et al.  Organ targeting In vivo using phage display peptide libraries , 1996, Nature.

[58]  T. Stehle,et al.  Immunoglobulin Superfamily Virus Receptors and the Evolution of Adaptive Immunity , 2009, PLoS pathogens.

[59]  W. Stallcup,et al.  NG2 Proteoglycan Promotes Endothelial Cell Motility and Angiogenesis via Engagement of Galectin-3 and α3β1 Integrin , 2004 .

[60]  Cunji Gao,et al.  Mechanisms of PECAM-1-mediated cytoprotection and implications for cancer cell survival , 2005, Leukemia & lymphoma.

[61]  I. Fidler,et al.  Characterization of the invasive and metastatic phenotype in human renal cell carcinoma , 1991, Clinical & Experimental Metastasis.

[62]  D. Galileo,et al.  Soluble L 1 CAM promotes breast cancer cell adhesion and migration in vitro , but not invasion , 2010 .

[63]  S. Hakomori Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. , 1996, Cancer research.

[64]  D. Peeper,et al.  Metastasis mechanisms. , 2009, Biochimica et biophysica acta.

[65]  S. Cai,et al.  Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells , 2011, BMC Cancer.

[66]  M. Bar‐eli,et al.  Expression of Id-1 is regulated by MCAM/MUC18: a missing link in melanoma progression. , 2011, Cancer research.

[67]  Y. van Kooyk,et al.  MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule). , 1998, The American journal of pathology.

[68]  C. Sorenson,et al.  PECAM-1 regulates proangiogenic properties of endothelial cells through modulation of cell-cell and cell-matrix interactions. , 2010, American journal of physiology. Cell physiology.

[69]  F. Balkwill Cancer and the chemokine network , 2004, Nature Reviews Cancer.

[70]  Leonid Nikitenko Vascular endothelium in cancer , 2008, Cell and Tissue Research.

[71]  Kenneth M. Yamada,et al.  Random versus directionally persistent cell migration , 2009, Nature Reviews Molecular Cell Biology.

[72]  C. Coffill,et al.  The role of mutant p53 in human cancer , 2011, The Journal of pathology.

[73]  C. Vens,et al.  Ectopic expression of NCAM in mouse fibroblasts stimulates self-aggregation, and promotes integration into primary cerebellum cell aggregates. , 1994, Cell adhesion and communication.

[74]  C. Horbinski,et al.  Live free or die: tales of homeless (cells) in cancer. , 2010, The American journal of pathology.

[75]  A. Barclay,et al.  Membrane proteins with immunoglobulin-like domains--a master superfamily of interaction molecules. , 2003, Seminars in immunology.

[76]  P. Friedl,et al.  Collective cell migration in morphogenesis, regeneration and cancer , 2009, Nature Reviews Molecular Cell Biology.

[77]  M. Rajesh,et al.  Novel Role of Lactosylceramide in Vascular Endothelial Growth Factor–Mediated Angiogenesis in Human Endothelial Cells , 2005, Circulation research.

[78]  R. Weinberg,et al.  A Perspective on Cancer Cell Metastasis , 2011, Science.

[79]  H. Müller-Hermelink,et al.  Novel RUNX1 isoforms determine the fate of acute myeloid leukemia cells by controlling CD56 expression. , 2007, Blood.

[80]  L. Liotta,et al.  General mechanisms of metastasis , 1997, Cancer.

[81]  Hong-yu Yang,et al.  Association of VCAM-1 overexpression with oncogenesis, tumor angiogenesis and metastasis of gastric carcinoma. , 2003, World journal of gastroenterology.

[82]  D. Lev,et al.  Cellular Adhesion Pathways and Metastatic Potential of Human Melanoma , 2002, Cancer biology & therapy.

[83]  J. Müller,et al.  Restoration of E-cadherin sensitizes human melanoma cells for apoptosis , 2006, Melanoma research.

[84]  A. Al-Mehdi,et al.  Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis , 2000, Nature Medicine.

[85]  R. Schreiber,et al.  Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion , 2011, Science.

[86]  T. Motyl,et al.  ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy. , 2006, Medical science monitor : international medical journal of experimental and clinical research.

[87]  Pengcheng Bu,et al.  Anti-CD146 monoclonal antibody AA98 inhibits angiogenesis via suppression of nuclear factor-κB activation , 2006, Molecular Cancer Therapeutics.

[88]  K. Umezawa,et al.  Involvement of autocrine CXCL12/CXCR4 system in the regulation of ovarian carcinoma cell invasion. , 2010, Biochemical and biophysical research communications.

[89]  J. Becker,et al.  Role of matrix metalloproteinases in melanoma cell invasion. , 2005, Biochimie.

[90]  K. Luzzi,et al.  Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. , 1998, The American journal of pathology.

[91]  K. Pienta,et al.  Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs. , 2005, Neoplasia.

[92]  K P Dingemans,et al.  Mechanisms of metastasis. , 1979, Biochimica et biophysica acta.