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 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 first funding period, we performed immunohistochemical analysis of DDR1 in 120 samples of invasive BrCa cases with different molecular subtypes and found a significant inverse association between cytoplasmic DDR1 localization and progesterone receptor expression in ER+ tumors. However, the limited number of primary tumors with match bone metastases compromised significance. In this period, we expanded the tissue collection to 42 new cases, which will be analyzed for DDR expression in the next period. In the period of this report, we tested the effect of a new small molecule DDR1kinase 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 the next period, we will utilize MDA-MB-231 cells with modified DDR expression in the intraosseous tumor model. We will also follow the proposed Tasks and investigate the role of tumor-associated DDRs on the regulation of pro- and anti-osteolytic genes in vitro.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2018
- Accession Number
- AD1055192
Entities
People
- Hyeong-reh Kim
- Rafael Fridman
Organizations
- Wayne State University