Discoidin Domain Receptors: Novel Targets in Breast Cancer Bone Metastasis
Abstract
Here we report major findings for our project aimed at studying the expression of Discoid in Domain Receptors (DDRs) in breast cancer (BrCa) tissues and their functional contribution to the formation of BrCa bone metastases. We also aimed at testing the feasibility of targeting DDRs for the treatment BrCa bone metastases. During the 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. We tested the effect of a new small molecule DDR1 kinase inhibitor in a model of intraosseous tumor growth using MCF7-Luc BrCa cells in mice supplemented with estrogen. These studies showed no significant effect of the inhibitor on intraosseous tumor burden between treated and untreated mice. A limitation of this study was the significant formation of bone observed in mice treated with estrogen, which limited tumor growth, and possibly affected tumor response to the inhibitor. In another model, MDA-MB-231 BrCa cells expressing wild type or kinase dead DDR1b were 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 (no DDR1b expression). Interestingly, expression of the kinase dead DDR1b restore tumor growth when compared to cells expressing the wild type 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2020
- Accession Number
- AD1127560
Entities
People
- Hyeong-reh Kim
- Rafael Fridman
Organizations
- Wayne State University