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.
van der Voort van Zyp
Jochem
J
Surgical Service (11S), John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI 48201-1932, USA.
Thamilselvan
Vijayalakshmi
V
Walsh
Mary
M
Polin
Lisa
L
Basson
Marc D
MD
D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009366:Neoplasm Seeding; D009368:Neoplasm Transplantation; D011312:Pressure; D011336:Probability; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000187:drug effects / Q000502:physiology*; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016392:Proto-Oncogene Proteins pp60(c-src); D019703:Calcineurin