Discoidin Domain Receptors: Novel Targets in Breast Cancer Bone Metastasis
Technical Report,01 Feb 2018,31 Jan 2019
Wayne State University Detroit United States
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Here we report major findings for our project aimed at studying the expression of Discoidin Domain Receptors DDRs in breast cancer BrCa tissues and their functional contribution to the formation of BrCa bone metastases. We also aim at testing the feasibility of targeting DDRs for the treatment BrCa bone metastases. During the current funding period, we identified and classified pair matched tissues of primary invasive BrCa cases and corresponding bone metastases, from which 12 cases were analyzed for DDR1 expression by immunohistochemistry IHC. These analyses revealed expression of membranous DDR1 in both primary and metastases of ductal carcinomas. Lobular carcinomas displayed mostly cytoplasmic DDR1 staining in both primary and metastatic tumors. We generated human MDA-MB-231 BrCa cells with ectopic expression of wild type and kinase dead DDR1b and wild type DDR2. The DDR1b-expressing cells were tested in a model of intraosseous tumor growth in mice in a preliminary experiment. The promising results of this study led to a second experiment with a larger group of mice. X-ray analyses suggest that DDR1b may diminish formation of osteolytic lesions. However, confirmation of this potential role of DDR1b in bone metastases awaits analyses of tumor burden and bone response by histomorphometry, which are ongoing. In the next period, we plan to conduct additional IHC studies with the human samples and complete the analyses of the bones from the mice inoculated with the MDA-MB-231 cells.
- Medicine and Medical Research