Spontaneous and induced differentiation of human melanoma cells.
Malignant melanoma cells can differentiate spontaneously in vivo and in vitro into cells with a finite lifespan. Analysis of differentiating cells from primary melanomas in culture revealed a flat, fibroblast-like morphology and expression of the fibroblast-associated marker leucine aminopeptidase (LAP). Differentiation was also observed in a minor sub-population of permanent cell lines derived from metastatic lesions. An experimental model of melanoma cell differentiation was then developed, using the pyrimidine analog bromodeoxyuridine (BUdR). BUdR-treated cells had a flat morphology, were contact-inhibited, had up to 20-fold increased surface area, expressed LAP, no longer proliferated anchorage-independently in soft agar, and 3 out of 4 cell lines were non-tumorigenic in athymic nude mice. Our results show that models of differentiation of melanoma cells can be established that help to define pathways of differentiation.
Valyi-Nagy
I
I
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Shih
I M
IM
Györfi
T
T
Greenstein
D
D
Juhasz
I
I
Elder
D E
DE
Herlyn
M
M
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D066298:In Vitro Techniques; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007931:Leucyl Aminopeptidase; D001973:Bromodeoxyuridine