Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice

Craig, David H., Owen, Cheri R., Conway, William C., Walsh, Mary F., Downey, Christina and Basson, Marc D. (2008) Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice. Journal of Clinical Investigation, 118 9: 3170-3180. doi:10.1172/JCI34279


Author Craig, David H.
Owen, Cheri R.
Conway, William C.
Walsh, Mary F.
Downey, Christina
Basson, Marc D.
Title Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
1558-8238
Publication date 2008-09-01
Sub-type Article (original research)
DOI 10.1172/JCI34279
Open Access Status DOI
Volume 118
Issue 9
Start page 3170
End page 3180
Total pages 11
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Language eng
Abstract Iatrogenic tumor cell implantation within surgical wounds can compromise curative cancer surgery. Adhesion of cancer cells, in particular colon cancer cells, is stimulated by exposure to increased extracellular pressure through a cytoskeleton-dependent signaling mechanism requiring FAK, Src, Akt, and paxillin. Mechanical stimuli during tumor resection may therefore negatively impact patient outcome. We hypothesized that perioperative administration of colchicine, which prevents microtubule polymerization, could disrupt pressure-stimulated tumor cell adhesion to surgical wounds and enhance tumor-free survival. Ex vivo treatment of Co26 and Co51 colon cancer cells with colchicine inhibited pressure-stimulated cell adhesion to murine surgical wounds and blocked pressure-induced FAK and Akt phosphorylation. Surgical wound contamination with pressure-activated Co26 and Co51 cells significantly reduced tumor-free survival compared with contamination with tumor cells under ambient pressure. Mice treated with pressure-activated Co26 and Co51 cells from tumors preoperatively treated with colchicine in vivo displayed reduced surgical site implantation and significantly increased tumor-free survival compared with mice exposed to pressure-activated cells from tumors not pretreated with colchicine. Our data suggest that pressure activation of malignant cells promotes tumor development and impairs tumor-free survival and that perioperative colchicine administration or similar interventions may inhibit this effect.
Keyword Focal adhesion kinase
Large-bowel cancer
Colon-cancer
Colorectal-cancer
Shear-stress
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Mon, 14 Mar 2011, 18:52:43 EST