EXPRESSION OF CD44 SPLICE VARIANTS IN HUMAN CUTANEOUS MELANOMA AND MELANOMA CELL-LINES IS RELATED TO TUMOR PROGRESSION AND METASTATIC POTENTIAL

Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of di fferent animal and human cancers. Because human cutaneous melanoma is among the most aggressive human cancers, we explored expression of CD4 4 isoforms (CD44v) in lesions of melanocytic tumor progression. In add ition, by RT-PCR and FACS analysis we assessed CD44v RNA species and c ell surface expression of CD44v in cultured melanocytes isolated from human foreskin and in a panel of 2 non-, 2 sporadically and 2 highly m etastatic human melanoma cell lines. We observed that all melanocytic lesions examined showed strong uniform expression of standard CD44 (CD 44s) epitopes. We did not detect CD44v6 expression in the melanocytic lesions. However, CD44 isoforms containing v5 or v10 were differential ly expressed. V5 was expressed in 16%, 0%, 20%, 67% and 58% of common nevi, atypical nevi, early primary melanomas (less than or equal to 1. 5 mm), advanced primary melanomas (>1.5 mm) and metastases, respective ly, and hence was related to tumor progression. In contrast, CD44v10 w as expressed in all common nevi, whereas part of the atypical nevi and most primary melanomas and metastases lacked v10. CD44v RNA patterns were closely similar in cultured melanocytes and all melanoma cell lin es. Melanocytes expressed high levels of CD44s but no CD44v, whereas a ll melanoma cell lines expressed CD44v at the surface. Interestingly, expression of v5 was strongly increased in the highly metastatic cell lines. Our results suggest a role for CD44 variant domains, particular ly v5 and v10, in human melanocytic tumor progression. (C) 1995 Wiley- Liss Inc.