Current Research Description

Dr. Sizemore’s research focuses on delineating the key molecular drivers of breast cancer subtype-specific phenotypes with special emphasis on the contributions of the tumorigenic and metastatic tumor microenvironment (TME). In addition, her team seeks to identify novel therapeutic targets to disrupt critical TME signaling. To achieve these goals, the lab combines novel mouse and cell line models of breast development and cancer with patient-derived tissue studies.

In searching for driver pro-metastatic pathways, the Sizemore lab uncovered a receptor tyrosine kinase, platelet derived growth factor receptor-beta (PDGFRβ), which promotes breast cancer metastasis in the brain [Thies et al. Cancer Research (2020)]. PDGFRβ is found primarily in mesenchymal cells of the breast tumor/metastatic microenvironment. This includes glial and perivascular lineages within the brain. In contrast, PDGFB, the ligand that preferentially activates PDGFRβ, is expressed by all endothelial cells and a subset of breast tumors. Importantly, primary breast tumors that express the ligand PDGFB have a propensity to recur in the brain. Current projects are delving into this novel tumor-stromal PDGFB-to-PDGFRβ signaling pathway to better understand how tumor-derived PDGFB mechanistically promotes breast cancer metastasis in the brain. This work is funded through the NIH and the Department of Defense Breast Cancer Research Program.