Accession Number : AD1035847


Title :   Discoidin Domain Receptors: Novel Targets in Breast Cancer Bone Metastasis


Descriptive Note : Technical Report,01 Feb 2016,31 Jan 2017


Corporate Author : Wayne State University Detroit United States


Personal Author(s) : Bonfil,Ricardo D ; Fridman,Rafael


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1035847.pdf


Report Date : 01 Feb 2017


Pagination or Media Count : 15


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 of 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. We plan to continue these tissue analyses to elucidate the significance of these findings, and to further examine the association between DDR expression in primary tumors and development of BrCa bone metastasis. In our experimental studies, we have screened and defined the expression and activation of DDRs in different human BrCa cell lines, confirmed the selectivity and inhibitory action of a new DDR1 tyrosine kinase inhibitor, and validated the ability of MCF7-Luc BrCa cells to grow within the tibiae of immunodeficient mice when supplemented with estrogen. With this information, we plan to test the role of DDR1 in intraosseous growth of these cells in mice treated with the kinase inhibitor. We will also test the role of DDR2 in intraosseous BrCa growth. The results of these studies will be used to investigate the role of tumor-associated DDRs on the regulation of pro- and anti-osteolytic genes in vitro.


Descriptors :   breast cancer , TISSUES (BIOLOGY) , gene expression , metastasis , neoplasms , cell lines , inhibitors , GENETIC MARKERS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE