Cell adhesion molecules in the development and progression of malignant melanoma

Cancer Metastasis Rev. 1999;18(3):345-57. doi: 10.1023/a:1006304806799.


Cell adhesion molecules belonging to the integrin, cadherin and immunoglobulin superfamilies have been implicated in tumor progression in cutaneous melanoma. Expression of the alpha v beta 3 integrin first appears with the change from radial to vertical growth, a step which is associated with the development of metastatic potential. VLA-4 expression is characteristic of advanced primary tumors and may mediate interaction of the tumor cells with VCAM-1 on vascular endothelium. Expression of these integrins is a marker of poor prognosis in patients and can confer invasive (alpha v beta 3) and metastatic (VLA-4) properties to human melanoma cells injected into nude mice. Expression of the immunoglobulin superfamily molecules MUC18/MCAM and ICAM-1 are associated with primary tumors and metastases. MUC18/MCAM expression confers metastatic potential and increased tumorigenicity to human melanoma cells. Expression of ICAM-1 has been shown to be a marker of poor prognosis in stage I tumors and interfering with its expression inhibits experimental metastasis by melanomas in nude mice. E-cadherin is used by epidermal melanocytes to interact with neighboring keratinocytes. Changes in E-cadherin expression and cellular localization is first observed in the radial growth phase, the earliest stage in melanoma development. Loss of E-cadherin function is associated with upregulation or induction of MUC18/MCAM and alpha v beta 3 in melanocytic cells in vitro and with alterations in the levels and cellular distribution of the transcriptional regulator beta-catenin in melanomas in vivo. These observations suggest that disturbances in E-cadherin function is not only important in carcinomas but may also be a critical event in melanoma tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, CD*
  • CD146 Antigen
  • Cadherins / analysis
  • Cadherins / physiology
  • Cell Adhesion Molecules / physiology*
  • Humans
  • Integrin alpha4beta1
  • Integrins / physiology
  • Melanoma / pathology*
  • Membrane Glycoproteins / physiology
  • Mice
  • Neural Cell Adhesion Molecules*
  • Receptors, Lymphocyte Homing / physiology


  • Antigens, CD
  • CD146 Antigen
  • Cadherins
  • Cell Adhesion Molecules
  • Integrin alpha4beta1
  • Integrins
  • MCAM protein, human
  • Mcam protein, mouse
  • Membrane Glycoproteins
  • Neural Cell Adhesion Molecules
  • Receptors, Lymphocyte Homing