Mechanical deformation induces proliferation of human colorectal carcinomacells

The cell biology of intravascular tumor cells is clinically important but t he many important variables of this environment have proved difficult to mo del. We studied the effects of repetitive mechanical deformation, a phenome non affecting all intravascular cells, on human colon cancer cell line HCT 116 in vitro. Cell proliferation, assessed by [H-3]-thymidine incorporation and cell count, increased by about 30% at two days in cells subjected to d eformation at 30 cycles/min as compared to controls; levels of the nuclear proliferation antigen detected by monoclonal antibody MIB-1 were also incre ased. Deformation increased transforming growth factor beta 1 (TGF-beta 1) and plasminogen activator inhibitor-1 gene expression sevenfold at two days , but mannose-6-phosphate did not affect cell proliferation, indicating tha t endogenous TGF-beta is not involved in the proliferative response. HCT 11 6 cells lack TGF-beta type II receptors, but stable transfection of TGF-bet a type II receptor cDNA did not alter the cellular response to mechanical d eformation, as assessed by cell proliferation, morphology, or gene expressi on. Mechanical deformation affects several important aspects of HCT 116 cel l biology, suggesting that the intravascular environment may regulate tumor cell biology in general. Endogenous TGF-beta and TGF-beta receptor-mediate d signaling are not responsible for the deformation-induced proliferative r esponse in HCT 116.