Dynamic heterogeneity: characterization of two cell lines derived from experimental lung metastases of mouse KHT fibrosarcoma.
We have recently demonstrated that KHT fibrosarcoma variant cells that form experimental metastases are generated by a stochastic process at high effective rates (approximately 10(-5)/cell/generation). The metastatic variant cells are unstable and are rapidly lost with an effective rate of reversion of approximately 10(-1)/cell/generation. In this study, we have examined the dynamics of generation of metastatic variant cells for two lines of KHT cells derived from individual experimental lung metastases in a single step selection. When grown in vitro, the KHT35-L1 cell population maintained a highly metastatic phenotype whereas the KHT3-L1c cell population reverted to a poorly metastatic phenotype. Our results indicate that there is an approximately 10-fold higher effective rate of generation of metastatic variant cells for KHT35-L1 cells relative to KHT3-L1c cells. Thus, a higher effective rate of generation of metastatic variants accompanies a stably expressed metastatic ability in fibrosarcoma cells and, as we have previously reported, in melanoma cells.
Harris
J F
JF
London Regional Cancer Centre, Ont., Canada.
Chambers
A F
AF
Ling
V
V
Hill
R P
RP
D000818:Animals; D002452:Cell Count; D002461:Cell Line, Transformed; D005354:Fibrosarcoma / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology*; D013269:Stochastic Processes