Combinatorial intervention of prostaglandin E2 receptor and calcium sensing receptor to attenuate breast cancer cell proliferation, migration and bone metastasis (Review)

Parkash,Jai; Asotra,Kamlesh

doi:10.3892/etm_00000036

Combinatorial intervention of prostaglandin E2 receptor and calcium sensing receptor to attenuate breast cancer cell proliferation, migration and bone metastasis (Review)

Authors:
- Jai Parkash
- Kamlesh Asotra
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Affiliations: Robert Stempel College of Public Health and Social Work, Department of Environmental and Occupational Health, Florida International University, Miami, FL 33199, USA
Published online on: March 1, 2010 https://doi.org/10.3892/etm_00000036
Pages: 227-231

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Abstract

The bone metastasis of breast cancer cells causes significant mortality among women, presumably through the enrichment of the bone microenvironment with growth factors and the stimulation of osteoclastic bone resorption, which leads to large increases in local extracellular calcium concentration, [Ca2+]0. These large increases in [Ca2+]0 are ‘sensed’ by the cancer cells as well as by osteoblasts, osteoclasts and monocytes. An extracellular calcium-sensing receptor (CaR) enables [Ca2+]0 to contribute directly to this vicious cycle by ‘transactivating’ an epidermal-growth factor receptor (EGFR) followed by the initiation of EGFR signaling and the up-regulation of parathyroid hormone-related peptide (PTHrP) in the breast cancer cells. Prostaglandins such as prostaglandin E2 (PGE2), which result from cyclooxygenase 2 (COX2) activity in stromal and breast cancer cells, also play an important role in the metastasis of breast cancer. The direct inhibition of the PGE2 receptor EP2 can serve as a better alternative to COX2 inhibition as a means for cancer prevention and treatment. Since EGFR can be ‘transactivated’ by both CaR and EP2, the resulting convergence of signaling cross-talk at the level of EGFR and PTHrP offers pharmacological interventional opportunities. We hypothesize that EP2 and CaR are coordinately involved in breast cancer cell proliferation, cell migration and bone metastasis. Our hypothesis suggests a rationale for therapeutic approaches directed against breast cancer metastasis to bone via combinatorial drug interventions of EP2 and CaR functions.

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