Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice.
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.
Craig
David H
DH
Department of Surgery, John D. Dingell VA Medical Center and Wayne State University, Detroit, Michigan 48201-1932, USA.
Owen
Cheri R
CR
Conway
William C
WC
Walsh
Mary F
MF
Downey
Christina
C
Basson
Marc D
MD
D000818:Animals; D045744:Cell Line, Tumor; D003078:Colchicine / Q000494:pharmacology*; D018572:Disease-Free Survival; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D011312:Pressure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*; D019061:src-Family Kinases / Q000378:metabolism
D051419:Paxillin; D050257:Tubulin Modulators; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D003078:Colchicine