Relationship Between Growth Rate and Differentiation of Melanoma In Vivo2

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Abstract
A study of growth rate and differentiation in a melanoma of the golden hamster is reported. Single melanoma cells isolated from subcutaneous tumors gave rise to 6 clonal lines. The growth rate and melanin content of the 6 clonal lines were compared after the third transplant generation. Two were slow growing and heavily pigmented; 4 were fast growing and lightly pigmented. This demonstrates the heterogeneity of the cell population of the original tumor and indicates that the progression of transplantable melanomas from slow-growing pigmented to fast-growing amelanotic neoplasms may be a selection of pre-existing cell types, as has been suggested by others. When these homogeneous lines were selected for their fastest growing cells by ascites conversion, marked increments in growth rate and decrements in melanin content were observed until the fastest growing tumors were amelanotic (undifferentiated). These data suggest that adaptive changes in response to the intraperitoneal environment may eventuate populations of cells capable of ascites conversion. Ultimately the changes become irreversible. The data support the concept that growth rate and differentiation, i.e., melanogenesis, are inversely related in this melanoma.