Shih I M, Elder D E, Hsu M Y, Herlyn M
Wistar Institute, Philadelphia, PA 19104-4268.
Am J Pathol. 1994 Oct;145(4):837-45.
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.
细胞间黏附受体Mel-CAM/MUC18在转移性黑色素瘤细胞上高度表达，在原发性黑色素瘤上也可检测到，但在正常黑素细胞上则无法检测到。先前的研究表明，Mel-CAM/MUC18表达的增加与肿瘤厚度和转移潜能相关。我们在此表明，培养中的正常黑素细胞和痣细胞表达Mel-CAM/MUC18，但当细胞与角质形成细胞共培养时，其表达会下调。角质形成细胞介导的对黑素细胞、痣细胞和早期黑色素瘤上Mel-CAM/MUC18表达的这种调节在患者标本中也可原位证实。另一方面，原发性和转移性病变的黑色素瘤细胞组成性表达Mel-CAM/MUC18，角质形成细胞没有调节作用。这些结果表明，角质形成细胞与人类黑素细胞之间的接触调节Mel-CAM/MUC18表达，这增加了在黑色素瘤发展过程中逃避角质形成细胞控制会导致有助于恶性表型的抗原表达的可能性。
