Showing papers by "Ie Ming Shih published in 1994"

Isolation and Functional Characterization of the A32 Melanoma-associated Antigen

Abstract: Cell surface melanoma-associated antigens can mediate cell-cell or cell-substrate adhesion, signal transduction, proteolysis, or immune recognition and play a key role in determining invasive and metastatic competence of the tumor cells. The melanoma-associated antigen, A32, was defined by a murine monoclonal antibody and was immunoprecipitated as a single 113 kDa integral membrane glycoprotein containing sialic acid and HNK-1 carbohydrate moieties. Immunohistochemistry revealed the presence of A32 antigen on most melanomas and nevi but not on normal epidermal melanocytes. Of the normal tissues tested, only endothelium, smooth muscle, cerebellum, and hair follicles expressed the A32 antigen. Tryptic peptides of the A32 antigen obtained after immunoaffinity chromatography showed sequence identity to MUC18 antigen, a member of the immunoglobulin supergene family. Melanoma cells adhered to affinity-purified A32 antigen immobilized to a solid phase, and the adhesion was blocked by either soluble A32 antigen or monoclonal antibody against the HNK-1 carbohydrate moiety. These findings, together with the observation that A32 antigen is concentrated in cell-cell contact borders, suggest that this antigen is an adhesion molecule with a possible role in tumor invasion and metastasis.

Regulation of Mel-CAM/MUC18 expression on melanocytes of different stages of tumor progression by normal keratinocytes.

Abstract: The cell-cell adhesion receptor, Mel-CAM/MUC18, is highly expressed on metastatic melanoma cells and is also detectable on primary melanomas but not on normal melanocytes. Previous studies have shown that increased Mel-CAM/MUC18 expression correlates with tumor thickness and metastatic potential. We show here that normal melanocytes and nevus cells in culture express Mel-CAM/MUC18, but expression is down-regulated when cells are co-cultured with keratinocytes. Such keratinocyte-mediated regulation of Mel-CAM/MUC18 expression on melanocytes, nevus cells, and early melanomas can also be demonstrated in situ in patients' specimens. On the other hand, melanoma cells from primary and metastatic lesions constitutively express Mel-CAM/MUC18, and keratinocytes have no modulatory effect. These results suggest that contact between keratinocytes and human melanocytic cells modulates Mel-CAM/MUC18 expression, raising the possibility that escape from keratinocyte control during melanoma development leads to expression of antigens that contribute to the malignant phenotype.