title: Increased metastases are associated with inflammation and matrix metalloproteinase-9 activity at incision sites in a murine model of peritoneal dissemination of colorectal cancer.
abstract: BACKGROUND
  Pro-inflammatory processes associated with the early postoperative state are known to contribute to peritoneal metastases in patients with advanced diseases. This study aimed to determine whether the wound healing response after an abdominal incision leads to increased matrix metalloproteinase (MMP)-9 activity locally, contributing to peritoneal metastasis.
  
  
  METHODS
  Metastatic tumors were initiated in C57bl/6J male mice (8wk of age) using a peritoneal injection model with syngeneic MC38 murine colon cancer cells; appropriate control mice also were studied. Injections were performed into the peritoneum in the right lower quadrant. We then observed the occurrence and rate of peritoneal metastasis for each group.
  
  
  RESULTS
  By making an incision into the abdominal wall of mice, an inflammatory response was induced at the wound site. The inflammatory response initiated by the wound, in turn, increased the proliferation of mesothelial cells and increased inflammatory cell numbers locally, which contributed to an increase in parietal peritoneal metastases. In addition, the wound healing process increased the expression of pro-inflammatory cytokines and the number of inflammatory cells in the peritoneum. Moreover, MMP-9 in the modeled postoperative injury setting increased the number and severity of peritoneal metastases.
  
  
  CONCLUSIONS
  Thus, we conclude that wound-associated inflammation enhances pro-MMP-9 expression, which plays a key role in the growth and progression of cancer cells associated with peritoneal metastases.
authors: Department of Surgery, St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors: In Kyu
authors: IK
authors: Lee
authors: Michael N
authors: MN
authors: Vansaun
authors: Jung Ho
authors: JH
authors: Shim
authors: Lynn M
authors: LM
authors: Matrisian
authors: D Lee
authors: DL
authors: Gorden
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007249:Inflammation / Q000209:etiology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010534:Peritoneal Neoplasms / Q000556:secondary*; D014945:Wound Healing
chemical_list: D020780:Matrix Metalloproteinase 9