Phenotypic stability of murine tumor cells in vitro and in vivo

Murine fibrosarcoma cells that vary in their transplantability in syngeneic mice were isolated from a heterogeneous parent tumor (induced in a female C57BL/6 inbred mouse) and maintained in culture by serial passage. Several biologic properties that discriminate between the high- and low-transplantable lines (including adhesiveness, motility, and levels of chymotrypsin-like esterase activity), as well as properties that do not separate these lines (e.g., in vitro growth rates and levels of protease and glycosidase activities), were measured at periodic intervals over 2 years. Ability to induce primary tumors and to induce metastases from these tumors were evaluated at the same intervals. The high- and low-transplantable lines were also transplanted into syngeneic mice at tumorigenic doses. Isolates from primary and metastatic tumors induced in the animals were reestablished in culture and examined for the various characteristics of passages 5, 10, 20, and 30. The properties of the cells maintained continually in culture remained stable throughout the 2-year observation period. Tumor isolates showed some evidence of modulation immediately after reestablishment in culture, but by passage 10 they appeared to be identical to the prototype parent lines. These data show that the fibrosarcoma cells do not undergo continual phenotypic "drift" as has been suggested to occur with other tumor lines maintained by serial passage in animals or in culture.