CELL-ADHESION MOLECULES OF THE IMMUNOGLOBULIN SUPERGENE FAMILY AND THEIR ROLE IN MALIGNANT TRANSFORMATION AND PROGRESSION TO METASTATIC DISEASE

Cell adhesion molecules (CAMs) of the immunoglobulin supergene family may play important roles in tumorigenesis and the development of metastatic disease. In a variety of human malignancies, tumor progression has been observed to be associated with changes in CAM expression. An early event in colorectal tumorigenesis appears to be the down regulation of a normally expressed CAM, DCC. Overexpression of a second CAM, carcinoembryonic antigen, is associated with colorectal tumors which have a high risk for metastasis development. Several tumors, including Wilms tumors and neuroblastoma, have been found to express a developmentally regulated form of NCAM which inhibits a variety of cell-cell interactions. Malignant cells not only show aberrations in the expression of their CAMS and thus their normal cell-cell interactions, but establish new adhesive interactions. The development of metastatic potential in cutaneous melanoma is associated with the de novo expression of two CAMs, one of which is ICAM-1, a molecule mediating adhesion between the tumor cells and leukocytes.