Emergence of hamster fibroblast XXXX in @entity19 --evidence for in vivo selection leading to loss of growth factor requirement.

@entity19 @entity5 @entity734 @entity3569
The @entity3569 lung fibroblast cell line (CC139) has high anchorage @entity734 for growth and has retained the high serum @entity734 of secondary cultures of adult fibroblasts. This cell line is tumorigenic in @entity19 ; however, the resulting @entity5 cells have different properties than those of the cell line injected. The @entity5 -derived cells had strongly reduced or even lost both the high anchorage and the high serum @entity734 of CC139 cells. This finding suggests that an in vivo selection is necessary for CC139 cells to acquire the malignant phenotype. After mutagenesis, which increases the frequency of CC139 colony formation in agarose up to 8-fold, we selected and analyzed 15 anchorage-independent colonies. No correlation between the colony-forming ability in agarose and serum-growth factor requirement for DNA synthesis was observed. Each of these clones were injected into @entity19 and the growth factor @entity734 of the ensuing @entity5 cells was compared to that of corresponding injected cells. All of the anchorage-independent colonies with the exception of one (A71), had acquired in vivo a stable phenotype allowing for partial or total escape of growth factor requirement. A71, the only clone which maintained the same growth factor requirement after two passages in vivo (A71 T1 and A71 T2) had already gained, in vitro, the minimal growth factor "relaxation" compatible with in vivo growth. A71 and A71 T1 @entity5 cells arrested in G0/G1 can reinitiate DNA synthesis in the presence of @entity19 plasma, low concentrations of serum, or thrombin. The fact that none of the @entity5 analyzed (more than 20) were found to have retained the high serum @entity734 of CC139 cells strongly suggests that the partial loss of serum growth factor requirement acquired in vivo is an essential malignant character for bypassing the hormonal growth restraints imposed by the host upon CC139 cells.
