title: Anti-beta1 integrin antibody reduces surgery-induced adhesion of colon carcinoma cells to traumatized peritoneal surfaces.
abstract: OBJECTIVE
  To study the mechanisms behind surgery-induced augmentation of tumor outgrowth.
  
  
  BACKGROUND
  Surgery provides the best chance of cure for most primary intra-abdominal carcinomas. Effective treatment is however relatively frequent complicated by peritoneal recurrences, which often originate from free-floating intraperitoneal tumor cells that implant on peritoneal surfaces. We previously reported that surgical trauma promotes development of peritoneal metastases.
  
  
  METHODS
  Evaluation of adhesion of CC531s rat colon carcinoma cell line intraperitoneally after laparotomy using in vivo, ex vivo, and in vitro models. Also, human ex vivo models were used to study peritoneal tumor cell adhesion.
  
  
  RESULTS
  Peritoneal imprints of operated rats showed that direct damaging of the peritoneum resulted in enhanced adhesion of rat CC531 colon carcinoma cells to submesothelial extracellular matrix (ECM) proteins in vivo, which was confirmed by electron microscopy. Additionally, the inflammatory reaction of the peritoneal cavity led to retraction of mesothelial cells, hereby also exposing ECM at peritoneal surfaces that had not been traumatized directly. Furthermore, we demonstrated that beta1 integrin subunits represented the primary mediators involved in adherence to either isolated ECM components or excised traumatized rat and human peritoneum. Importantly, incubation of CC531s cells with anti-beta1 integrin antibodies resulted in a significant decrease of tumor cell adhesion in vivo.
  
  
  CONCLUSIONS
  Surgical trauma results in exposure of ECM at directly and nondirectly damaged peritoneal surfaces, leading to increased beta1 integrin-dependent tumor cell adhesion. Perioperative therapies, which aim to block beta1 integrin subunits, might therefore serve as new clinical tools for the prevention of peritoneal recurrences.
authors.affiliation: Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Oosterling
authors.forename: Gerben J
authors.initials: GJ
authors.lastname: van der Bij
authors.forename: Marijn
authors.initials: M
authors.lastname: Bögels
authors.forename: Sander
authors.initials: S
authors.lastname: ten Raa
authors.forename: Jan A
authors.initials: JA
authors.lastname: Post
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: Marjolein
authors.initials: M
authors.lastname: van Egmond
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000601:surgery*; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010537:Peritoneum / Q000293:injuries*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000906:Antibodies; D019012:Integrin beta1