Discoidin Domain Receptors: Novel Targets in Breast Cancer Bone Metastasis
Technical Report,01 Feb 2016,31 Jan 2020
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 pairs of BrCa samples from primary tumors and bone metastases. We performed studies to examine DDR1 expression. We found high levels of membranous DDR1 in both primary and metastatic cancer cells. MDA-MB-231 BrCa cells expressing wild type or kinase dead DDR1bwere tested in a model of intraosseous tumor growth in female SCID mice. Histomorphometry analyses revealed that wild type DDR1b-expressing MDA-MB-231 cells displayed a tendency toward reduced intraosseous tumor burden when compared to control cells noDDR1b expression. Interestingly, expression of the kinase dead DDR1b restore tumor growth when compared to cells expressing the wildtype receptor. These results suggest that DDR1b may reduce the ability of MDA-MB-231 to grow within bone, and that this process requires kinase activity. We are conducting more analyses of the bone sections to confirm DDR1b expression and activation by immunohistochemistry. We are also conducting additional analyses to analyze bone response.
- Medicine and Medical Research