EXPRESSION OF CD44 VARIANT ISOFORMS IN MALIGNANT-MELANOMA

In a variety of human tumors, expression of splice variants of the adh esion molecule CD44 (CD44v) has been described as correlating with tum or progression. Here, we report on the expression of CD44v in melanocy tes, nevi, primary melanomas, and cutaneous and lymph node metastases. Thirteen nevi, 65 primary melanomas of varying thickness, 39 cutaneou s and 15 lymph node metastases, and melanocytes and a panel of melanom a lines were tested for surface expression of the standard form of CD4 4 and the variant exons v5, v6, v7, v7-v8, and v10 by immunohistology or fluorescence-activated cell sorting. Melanocytes did not express an y variant isoform of CD44. However, nevi, as well as primary melanoma and melanoma metastases, stained to a varying degree with anti-CD44v5, anti-CD44v7-v8, and anti-CD44v10. Exons v6 and v7 were not detected o n any of these tissue specimens. Compared with nevi, expression of exo n v10 was up-regulated in thick primary tumors and skin metastases. Ly mph node metastases displayed elevated levels of exon v5. Expression o f CD44v in melanoma lines (n = 20) differed, inasmuch as many lines di d not express variant isoforms; in particular, exon v10. Interestingly , however, the few CD44v5-positive melanoma lines metastasized in the nu/nu mouse. Because benign as well as malignant growth of melanocytes was accompanied by expression of CD44 variant isoforms, a linkage bet ween expression of CD44 variant isoforms and malignant transformation or tumor progression was excluded. Considering the function of distinc t isoforms, one might speculate that expression of exon CD44v5, which was up-regulated in lymph node metastases compared with nevi and prima ry melanoma, provided a growth stimulus. Exon v10 is present at high d ensity in epidermal cells. The de novo expression of this exon in nevi and the increased expression in thick melanoma and skin metastases wo uld be in Line with the assumption of an anchoring advantage in the su rrounding epidermal tissue.