title: Divalent cations influence colon cancer cell adhesion in a murine transplantable tumor model.
abstract: BACKGROUND
  Cancer cells adhere principally by integrins, matrix receptors that may be influenced by divalent cations. Surgical wound fluid is high in Mg2+ and low in Ca2+. We hypothesized that Mg+ and Mn2+ promote perioperative adhesion of shed cancer cells to surgical sites and that washing surgical wounds with Ca2+ inhibits implantation.
  
  
  METHODS
  We tested our hypothesis in a murine colon 26 adenocarcinoma model. We added 10 mmol/L CaCl2, 0.25 mmol/L MgCl2, or 0.5 mmol/L MnCl2 to suspended murine colon 26 cancer cells and placed these suspensions into wounds in anesthetized mice. After 30 minutes, we washed away nonadherent cells. In some studies, we 51Cr-labeled the cells and assayed tumor adhesion by wound radioactivity. In parallel studies, we closed the wounds and observed the mice for 90 days.
  
  
  RESULTS
  Mg2+ increased adhesion to 188% +/- 15% of control (n = 10, P < .001) and Mn2+ to 130% +/- 6% (n = 7, P < .001). However, Ca2+ inhibited adhesion to 61% +/- 12% (n = 7, P = .006) of control. Seventy-two percent of survival controls developed tumors during follow-up. Mg2+ and Mn2+ stimulated tumor formation to 96% and 92%, respectively, but adding Ca2+ to the wounds reduced subsequent tumor formation to 56% without altering serum Ca2+. The survival curves each differed significantly by log-rank test (P < .01 each). All pair-wise multiple comparisons were significant (Holm-Sidak, P < .05 each).
  
  
  CONCLUSIONS
  Thus, the high Mg2+ in endogenous wound fluid may potentiate tumor cell adhesion. However, 10 micromol/L Ca2+ inhibits cancer cell adhesion to murine wounds and subsequent tumor development. Irrigating with dilute CaCl2 could decrease local tumor recurrence by inhibiting the adhesion of shed tumor cells.
authors.affiliation: Wayne State University, John D. Dingell VAMC, 4646 John R. Street, Detroit, MI 48201-1932, USA.
authors.forename: Jochem
authors.initials: J
authors.lastname: van der Voort van Zyp
authors.forename: William C
authors.initials: WC
authors.lastname: Conway
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Thamilselvan
authors.forename: Lisa
authors.initials: L
authors.lastname: Polin
authors.forename: Marc D
authors.initials: MD
authors.lastname: Basson
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D002118:Calcium / Q000097:blood / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D008274:Magnesium / Q000097:blood / Q000494:pharmacology*; D008345:Manganese / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
chemical_list: D002413:Cations, Divalent; D008345:Manganese; D008274:Magnesium; D002118:Calcium