Calcium, calcium-sensing receptor and growth control in the colonic mucosa.

A role for calcium in epithelial growth control is well-established in the colon and other tissues. In the colon, Ca²+ "drives" the differentiation process. This results in sequestration of β-catenin in the cell surface / cytoskeletal complex, leaving β-catenin unavailable to serve as a growth-promoting transcription enhancer in the nucleus. The signaling events that lead from Ca²+ stimulation to differentiation are not fully understood. A critical role for the extracellular calcium-sensing receptor (CaSR) is assumed, based on CaSR localization to the differentiating epithelial cells in the normal colonic mucosa (upper half of the crypt and crypt surface), decreased CaSR expression in colon carcinoma, and the results from in vitro studies with colonic epithelial cell lines. While Ca²+ is well-accepted as a growth-regulating agent in the colon, suppression of cell proliferation is not complete. At least part of the reason for this is the inherent variability in Ca²+ responsiveness among individual epithelial cells. Of interest, colon epithelial cells that are resistant to the growth-regulating activity of Ca²+ alone are still responsive to Ca²+ in conjunction with other transition metals. Whether a multi-mineral approach will, ultimately, prove to be more effective than Ca²+ alone as a colon cancer chemopreventive agent remains to be seen, but certainly worth investigating.