Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice
David H. Craig, … , Christina Downey, Marc D. Basson
David H. Craig, … , Christina Downey, Marc D. Basson
Published August 14, 2008
Citation Information: J Clin Invest. 2008;118(9):3170-3180. https://doi.org/10.1172/JCI34279.
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Research Article Oncology

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

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.

Authors

David H. Craig, Cheri R. Owen, William C. Conway, Mary F. Walsh, Christina Downey, Marc D. Basson

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Figure 8

Effect of colchicine on tumor cell proliferation.

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Effect of colchicine on tumor cell proliferation. Co26 tumor cell prolif...
Co26 tumor cell proliferation was assessed by BrdU incorporation, PCNA immunohistochemistry, and MTT reduction after i.p. colchicine treatment. (A) In vivo BrdU incorporation in Co26 tumors 24 and 96 hours after treatment with colchicine. (B) Immunohistology of PCNA-positive tumor cells 20 days after implantation following treatment with colchicine or DMSO and exposure to either ambient pressure or 15 mmHg increased pressure. Original magnification, ×40. (C) At 12 hours after in vivo tumor treatment with colchicine or DMSO, isolated Co26 cells were exposed to either ambient pressure or 15 mmHg increased pressure. In vitro cell proliferation of the respective populations was assessed by colorimetric analysis of MTT reduction every 24 hours. Data are graphically expressed as mean ± SEM. *P < 0.05 compared with respective DMSO-treated control.