Extracellular pressure stimulates colon cancer cell adhesion in vitro and to surgical wounds by Src (sarcoma protein) activation.

BACKGROUND

We hypothesized that pressure stimulates colon cancer cell adhesion to surgical wounds.

METHODS

We quantitated adhesion of murine 26/51 transplantable colon cancer cells by cell counting or chromium 51-labeling. Tumor cells were added to murine surgical wounds after 30 minutes preincubation under ambient or 15 mm Hg increased pressure. Src activation was assayed by immunoblotting for phosphorylated Src and inhibited by 4-amino-5-(4chlorophenyl)-7-(t-butyl)pyrazolo-[3-4-d]pyrimidine (PP2).

RESULTS

Pressure stimulated colon 26/51 cell adhesion to murine wounds by 43% to 52% (n = 9, P <0.05 each). Pressure stimulated Src phosphorylation by 39% +/- 4% (n = 5, P = 0.004) in colon 26 cells. The Src inhibitor PP2 (20 mumol/L) did not inhibit Src phosphorylation at ambient pressure but prevented pressure stimulation of Src phosphorylation. Src blockade by PP2 did not affect basal adhesion of either tumor to murine wounds but completely blocked pressure stimulation of adhesion (n = 4, P <0.001 each).

CONCLUSIONS

Increased pressure may activate cancer adhesion to surgical wounds via Src. Src antagonists might inhibit this process.