Divalent cations influence colon cancer cell adhesion in a murine transplantable tumor model

Cancer cells adhere principally by integrins, matrix receptors that may be influenced by divalent cations. Surgical wound fluid is high in Mg 2+ and low in Ca 2+. We hypothesized that Mg + and Mn 2+ promote perioperative adhesion of shed cancer cells to surgical sites and that washing surgical wounds with Ca 2+ inhibits implantation. We tested our hypothesis in a murine colon 26 adenocarcinoma model. We added 10 mmol/L CaCl 2, 0.25 mmol/L MgCl 2, or 0.5 mmol/L MnCl 2 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. Mg 2+ increased adhesion to 188% ± 15% of control (n = 10, P < .001) and Mn 2+ to 130% ± 6% (n = 7, P < .001). However, Ca 2+ inhibited adhesion to 61% ± 12% (n = 7, P = .006) of control. Seventy-two percent of survival controls developed tumors during follow-up. Mg 2+ and Mn 2+ stimulated tumor formation to 96% and 92%, respectively, but adding Ca 2+ to the wounds reduced subsequent tumor formation to 56% without altering serum Ca 2+. 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). Thus, the high Mg 2+ in endogenous wound fluid may potentiate tumor cell adhesion. However, 10 μmol/L Ca 2+ inhibits cancer cell adhesion to murine wounds and subsequent tumor development. Irrigating with dilute CaCl 2 could decrease local tumor recurrence by inhibiting the adhesion of shed tumor cells.