Research Area
Breast cancer, mammary gland development, tumor-stromal interactions, tumor microenvironment, metastatic progression (specifically to the brain), novel stromal-specific cancer therapeutics
Research Summary
Breast tumors are surrounded by and in contact with many types of non-cancer cells, including fibroblasts, pericytes, immune cells and adipocytes. These surrounding cells are collectively termed the “tumor microenvironment” (TME), and the interplay between tumor cells with these nearby non-tumor cells greatly affects all steps of cancer progression.
Research in the Sizemore Lab focuses on novel factors in both the primary breast TME and in the metastatic microenvironment that we predict could be utilized as biomarkers/therapeutic targets to more effectively treat patients with breast cancer.
In searching for driver pro-metastatic pathways, our analyses uncovered a receptor tyrosine kinase, platelet derived growth factor receptor-beta (PDGFRβ), that we believe functions in the initiation and/or growth of breast cancer brain metastases. PDGFRβ is found primarily in cells of the breast tumor/metastatic microenvironment, while its ligand, PDGF-B, is expressed primarily by the breast tumor cells. Importantly, breast cancer brain metastases arise in ~10-20% of all metastatic breast cancer patients, and due to the complete lack of approved treatments for these patients, only one-fifth will still be living one year after their diagnosis. Our current work aims to address this important clinical problem through use of both in vitro cell line and in vivo mouse modeling of PDGF-B to PDGFRβ signaling in the TME. Additional projects in the lab focus on PDGFRβ and other stromal factors in normal mammary gland development.