Immunohistological methods were used to examine the relation between the metastatic potential of melanoma and expression of the neuroglandular antigen (CD63) and other members of this family of molecules, CD53, CD37, CD9 and the target of an anti-proliferative antibody (TAPA-I), as well as MHC-class-I and -II antigens. The criteria used to establish metastatic potential were their relation to thickness of the primary melanoma, and differences in expression between vertical and radial growth phases of primary melanoma and between primary and metastatic melanoma. Studies on basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) were also included as controls for malignant skin cancers with low metastatic potential. Expression of CD9 and MHC-class-I antigen was found to be inversely related to thickness of the primary tumor, and CD9 was expressed predominantly on primary rather than on metastatic tumors. CD9 expression correlated with MHC-class-I expression on melanoma, and both were expressed on BCCs and SCCs having low metastatic potential, but not on compound nevi. CD63 and TAPA-I were expressed on nevi but not on SCC and BCC. Leu 13 is a molecule associated with TAPA-I in lymphomas, and was found to be expressed in sections from 5 out of 34 primary and 5 out of 21 metastatic melanoma. CD53 and CD37 were not detected on melanoma. Our results indicate that several members of the neuroglandular antigen are expressed in melanoma and that low expression of CD9 on primary melanomas might have prognostic significance with respect to the potential for metastasis.
The induction of T-cell responses against tumor cells is believed to depend on both recognition of antigen and receipt of co-stimulatory signals from interaction of ligands such as B7 with its receptors CD28 or CTLA-4 on T cells. In the present study the expression of B7 on cultured human melanoma cells was studied at the mRNA level by reverse PCR analysis and surface expression by flow cytometric analysis with monoclonal antibodies (MAbs). PCR analysis revealed mRNA for B7 in 3 of 6 (50%) cultured primary melanoma and 8 of 19 (42%) cultures of metastatic melanoma. Analysis of B7 expression by flow cytometry using the BB1 MAb revealed low levels of expression in 3 of 10 melanoma that had mRNA for B7. In 2 of the latter (but not 4 other PCR+ lines) expression could be increased by culture in GM-CSF, IL-2, IFN-gamma and IFN-alpha 2. Our results indicate that although mRNA for B7 is present in 40-50% of melanoma cell lines, expression at the protein level is at low or undetectable levels in the majority of the cell lines. Expression of B7 protein was also not detected in studies on tissue sections from 11 primary and 9 metastatic melanomas.
We have previously shown that one of the co-factors required for generation of T-cell responses, B7.1, is variably expressed on melanoma cells. In the present studies we have examined the expression of another important co-factor in T-cell responses, viz., CD40, and investigated regulation of its expression and possible function(s). PCR analysis revealed mRNA for CD40 in all 18 cell lines established from metastatic melanoma and the majority of those from 6 primary melanoma. CD40 protein was detectable in approximately 50% of the cell lines by flow cytometry and in sections from only 2 of 20 melanoma. Expression of CD40 protein was increased in 2 of 3 cell lines with constitutive CD40 expression by interferon-gamma but not by granulocyte/macrophage colony-stimulating factor, interleukin-2 or tumor necrosis factor-alpha. Interaction of monoclonal antibody with CD40 on melanoma cells resulted in an increase in their cell division but did not increase expression of the costimulatory factor B7. Our results suggest that CD40 expression on melanoma may have important effects on their biology. The influence of CD40 expression on T-cell responses to melanoma remains to be investigated.
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