Calcium ions and the control of proliferation in normal and cancer cells

Abstract

Several lines of evidence suggest tha Ca2+ ions control cell proliferation: Ca2+ entry into cytoplasm acts as a general mitogen; serum and serum-replacements induce Ca2+ influx; the Ca2+ concentrations in growth media required to support the proliferation of normal cells are much higher than those required for cancer cells; serum and growth factors reduce the Ca2+ requirements of normal cells; tumour promoters alter Ca2+ fluxes via a mechanism used principally by growth factors. Minor supporting evidence includes the effects of various drugs and viruses, and the behaviour of tumour cell mitochondria and intercellular junctions. It is still not possible to decide exactly where and when inside cells the critical effect of Ca2+ on proliferation occurs, but we discuss at length the practical problems of understanding Ca2+ movements in tissue-culture cells. Carried to its logical conclusion, present evidence suggests that an overridden or bypassed Ca2+ control process may be the key, common determinant of unrestrained proliferation in cancer cells.

<b>ACUTE AND LONG-TERM EFFECTS OF GLUCOSE ON THE FUNCTION OF TRANSPLANTABLE RAT INSULINOMA CELLS MAINTAINED IN TISSUE </b><b>CULTURE </b>

“…It is possible that cyclic AMP sensitises the secretory machinery to Ca" to elicit insulin release (14). However, in common with other cancer cells (6), cultured insulinoma cells already exhibit extreme sensitivity to Ca" as witnessed by the independence of insulin release on extracellular Ca" (26). It therefore seems likely that the effect of theophylline is mediated through other mechanisms, possibly related to the ability of cyclic AMP to activate protein kinases in B-cells (13).…”

Involvement of l(–)-rhamnose in sea urchin gastrulation: a live embryo assay

“…Studies have shown that when cells are grown in vitro in media that lacked calcium, the cells disaggregated (Khurrum et al, 2004, Humphreys, 1963. Other studies have demonstrated that cancer cells contain half the amount of calcium than normal cells (Durham and Walton, 1982). This provides evidence that low calcium concentrations are important for altered cancer cell adhesions (Durham and Walton, 1982); therefore, media containing low calcium concentrations are important when conducting research involving embryonic cell adhesion mechanisms.…”

Network-based analysis of calcium-binding protein genes identifies Grp94 as a target in human oral carcinogenesis

“…Under physiologic conditions, many aspects of these processes are mediated by members of the Ca 2 þ -binding protein (Nelson and Chazin, 1998). Since considerable evidence shows that intracellular Ca 2 þ deregulation is crucial for tumour growth and development (Durham and Walton, 1982;Huang et al, 2005;Ding et al, 2006;Thebault et al, 2006), understanding the genetic mechanisms of the Ca 2 þ -binding protein genes involved in carcinogenesis is imperative for the development of new therapeutic strategies.…”