Mechanical deformation induces proliferation of human colorectal carcinoma cells.
The cell biology of intravascular tumor cells is clinically important but the many important variables of this environment have proved difficult to model. We studied the effects of repetitive mechanical deformation, a phenomenon affecting all intravascular cells, on human colon cancer cell line HCT 116 in vitro. Cell proliferation, assessed by [3H]-thymidine incorporation and cell count, increased by about 30% at two days in cells subjected to deformation at 30 cycles/min as compared to controls; levels of the nuclear proliferation antigen detected by monoclonal antibody MIB-1 were also increased. Deformation increased transforming growth factor beta1 (TGF-beta1) and plasminogen activator inhibitor-1 gene expression sevenfold at two days, but mannose-6-phosphate did not affect cell proliferation, indicating that endogenous TGF-beta is not involved in the proliferative response. HCT 116 cells lack TGF-beta type II receptors, but stable transfection of TGF-beta type II receptor cDNA did not alter the cellular response to mechanical deformation, as assessed by cell proliferation, morphology, or gene expression. Mechanical deformation affects several important aspects of HCT 116 cell biology, suggesting that the intravascular environment may regulate tumor cell biology in general. Endogenous TGF-beta and TGF-beta receptor-mediated signaling are not responsible for the deformation-induced proliferative response in HCT 116.
Johnson
F E
FE
Department of Surgery, Saint Louis University Health Sciences Center, Saint Louis, MO 63110-0250, USA.
Zhou
M
M
Collins
B T
BT
Huang
J S
JS
D002455:Cell Division; D015179:Colorectal Neoplasms / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013314:Stress, Mechanical; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013936:Thymidine