Extracellular calcium promotes the migration of breast cancer cells through the activation of the calcium sensing receptor

Calcium-sensing Receptor Modulates Cell Adhesion and Migration via Integrins

“…Recent studies have implicated the CaSR in the regulation of cell migration in the developing nervous system and in cancer metastasis (9,15). Here, we identified the integrins as key protein interaction partners with the functionally active CaSR endogenously expressed in rat medullary thyroid carcinoma cells.…”

“…Breast and prostate tumor cells also metastasize to bone; 65-75% of advanced breast and prostate cancer patients have secondary tumors in bone, with a 5-year survival rate of only 20 -25% (67). Interestingly, the CaSR has been shown to enhance the metastatic potential in various bone-preferring breast and prostate cancer cell lines (15,16,68). For example, in vitro experiments have revealed that blocking CaSR function in PC3 prostate cancer cells and MDA-MB-231 breast cancer cells inhibits cell adhesion and migration (15,16).…”

“…Several studies have demonstrated that the endosteal surface provides a niche for CaSR-expressing hematopoietic stem cells to preferentially localize to the bone and that hematopoietic stem cells prepared from mice lacking the CaSR were defective in localizing to the endosteal niche due to defective adhesion to the extracellular matrix protein, type I collagen (12,13). Finally, a potential role of the CaSR in tumor metastasis is suggested by studies showing the expression of the CaSR in prostate and breast cancer cells that preferentially metastasize to bone (15,16) and that the elevated Ca 2ϩ concentrations detected by the CaSR on highly metastatic, bone-preferring cancer cells have been shown to provide a strong chemo-attractant factor for cancer cell metastasis to bone cells (15,17).…”

Ca2+ chemotaxis inDictyostelium discoideum

“…Osteoblasts have been shown to undergo chemotaxis in Ca 2+ gradients in vitro as well as in platelet-derived growth factor (PDGF) gradients in vitro (Sugimoto et al, 1993;Godwin and Soltoff, 1997), and monocytes have been shown to undergo chemotaxis in Ca 2+ as well as in chemokine gradients in vitro (Olszak et al, 2000). In addition, macrophages and macrophage-derived foam cells, which are involved in generating atherosclerotic lesions (Shi et al, 1996), and prostate and breast cancer cells also undergo chemotaxis in spatial gradients of Ca 2+ in vitro (Liao et al, 2006;Saidak et al, 2009). Finally, Brokaw (Brokaw, 1974) demonstrated that bracken fern spermatozoids undergo chemotaxis in combinatorial gradients of Ca 2+ and bimalate.…”

CASR (Calcium-Sensing Receptor)

“…Both breast and prostate cancer cells that express the CaSR at high levels have a greater tendency to metastasize to bone than those that express the receptor at low levels (Liao et al, 2006;Mihai et al, 2006). High Ca 2+ concentrations act as a chemoattractant for breast cancer cells and this CaSR-dependent response positively correlates with the in vivo metastatic potential of several breast cancer cell lines (Saidak et al, 2009). In addition, high Ca 2+ at bony metastases signalling through the CaSR may stimulate further growth of malignant cells, for example by activation of choline kinase and production of phosphocholine (Huang et al, 2009 ) or by regulating estrogen receptor-α expression and activity (Journe et al, 2004).…”