Project 10 - Role of the CaSR in early bone metastasis of breast cancer cells and evaluation of CaSR - based therapeutics in prevention or delay of metastasis formation

Host Institution: Université de Picardie Jules Vernes
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Hypothesis: CaSR is a determinant of osteolytic breast cancer metastases. Activation of the CaSR in breast cancer cells is facilitated by high Ca²⁺_o and /or other molecules which are present in bone microenvironment.

Objectives: ESR_UPJV will 1) Investigate the role of CaSR in breast cancer cell migration in vitro, using MDA-MB-231 and MCF-7 breast cancer cells overexpressing the wild-type form of the CaSR or a dominant negative mutant of the receptor. Ca²⁺_o as well as hydroxyapatite will be used as chemoattractant factor. 2) Characterise the role of the CaSR in early bone metastatic event (metastatic stem cells) ex vivo, following bone marrow invasion of zeocin resistant MDA-MB-231 and MCF-7 cells after intracardiac and fat pad injection. 3) Investigate bone targeting potential of chemical modulators of the CaSR in nude mice using MALDI-Mass Spectrometry Imaging after intracardiac injection of breast cancer cell lines.