Histologic variation among experimental tumors of common origin: relationships to viral p21 expression and to tumor-derived extracellular matrix

Transformed lines, obtained by infection of adult rat adrenocortical fibroblast-like cells with Kirsten murine sarcoma virus, produce s.c. tumors which range histologically from fibrosarcomas to carcinomas to undifferentiated neoplasms. This study was undertaken to determine whether the histology was a stable characteristic of individual lines and whether it was related to oncogene expression and to differentiation in culture. Three lines were infected at passage 1 and tumor histology, differentiation markers and expression of the transforming protein v-p21 were evaluated periodically over a 1-year period. The original stromal characteristics of the target cells (metachromatic extracellular matrix (ECM), a high rate of collagen production and collagen incorporation into ECM, and a fibroblastic morphology) diminished with transformation. In contrast, parenchymal differentiation markers (lipid, steroidogenic enzymes) were enhanced and constitutively expressed in all lines. The two lines in which ECM production was most reduced formed carcinomas in vivo, while the third line showed a smaller shift in these characteristics and formed sarcomas. Thus, histopathology seemed to be influenced by tumor-derived ECM but unrelated to the expression of steroidogenic properties. The tumors became less differentiated with time, but retained distinct line-specific phenotypes. Throughout the study, v-p21 remained overexpressed in all lines to a similar degree, but the subcellular localization of v-p21 differed between fibroblastic and epithelial cells, suggesting a possible correlation with differentiation.