N-ras dependent revertant phenotype in human HT1080 fibrosarcoma cells is associated with loss of proliferation within normal tissues and expression of an adult membrane antigenic phenotype

Abstract

To investigate how the activated N-ras oncogene contributes to the tumorigenic potential of malignant human fibrosarcoma HT1080 cells we analysed the behavior of the parental cell line and of two flat revertants (1c and 10a) in an organ culture assay for invasion. In this assay the two revertants retain the ability of HT1080 cells to migrate within the chick cardiac muscle but lose the capacity to proliferate and to replace the normal tissue. Moreover the reversion of tumorigenic potential is associated with an evolution from an oncofoetal membrane antigenic pattern towards expression of a normal adult phenotype. Both the 4F2 antigen, which is implicated in the control of HT1080 cell proliferation, and heterodimers of the two chains (alpha and beta) of the IL2 receptor (IL2-R) are expressed in embryonic and HT1080 cells, but not in normal adult fibroblasts or in the revertant cell lines. For the first time in a non-lymphoid environment, we have detected a complex between the two IL2-R chains, together with a new species of mRNA (2.8 kB) from the IL2-R alpha gene. The behavior of these membrane markers strengthens the hypothesis that HT1080 cells may represent a block in the differentiation pathway of fibroblastic cells.