Neoplastic progression evidenced in the L929 cell system. I. Selection of tumorigenic and metastasizing cell variants.

Starting with a L929 cell strain of low tumorigenicity, and through in vivo and combined in vivo--in vitro manipulation, we have isolated a number of related culture cell lines with different tumorigenicity and metastasis ability in C3HA/H mice. Within our system, tumorigenicity can be greatly enhanced without the simultaneous development of metastasis ability, the latter arising only after long-term in vivo serial transplantation. Metastatic variants express better the ability to undergo to cascade of metastasis than the primary tumor. The selection of metastatic variants from a tumor, using its subcutaneous inoculation, renders cell lines with different behavior. Finally, viable cells are recovered from lungs of animals inoculated with metastatic variants that would not be expected to show true metastatic foci; the results are commented in relation to the phenomenon of metastasis dormancy. Our experiments are discussed under the scope of the hypothesis of neoplastic progression as a multistep process.