Divalent cations influence colon cancer cell adhesion in a murine transplantable tumor model.
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.
van der Voort van Zyp
Jochem
J
Wayne State University, John D. Dingell VAMC, 4646 John R. Street, Detroit, MI 48201-1932, USA.
Conway
William C
WC
Thamilselvan
Vijayalakshmi
V
Polin
Lisa
L
Basson
Marc D
MD
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
D002413:Cations, Divalent; D008345:Manganese; D008274:Magnesium; D002118:Calcium