Cancer Stromal Cells and Lymphovascular Invasion
Null, Jamie, Microbiology - School of Medicine, University of Virginia
Dudley, Andrew, MD-MICR Microbiology, University of Virginia
Breast cancer is the most commonly diagnosed cancer worldwide and is the leading cause of cancer-related mortality among women. Although existing therapeutic strategies are relatively effective at controlling localized disease, metastatic breast cancer that has spread to distant organs remains incurable and is responsible for the overwhelming majority of breast cancer-related deaths. In breast cancer metastasis, cancer cells escape from the primary tumor and enter circulation via the vasculature, allowing them to reach distant organs such as the lymph nodes, lungs, liver, bones, and brain and colonize these tissues. Standard therapies often fail to eliminate metastatic lesions, allowing for cancer outgrowth at these sites that compromises organ function and causes patient mortality. The lack of therapeutic options for metastatic disease can be attributed to the biological complexity of the metastatic process. Cancer cell invasion and entry into vessels is dynamic and driven by cross-talk between cancer cells and stromal cells within the tumor microenvironment, but the specific contributions of stromal populations are diverse and not fully understood. Therefore, we used in vivo genetic tools and in vitro functional assays to label and deplete a population of stromal cells marked by the expression of periostin, a matrisomal protein associated with metastasis, in order to characterize their functions during breast cancer progression. We report that highly-metastatic cancer cells activate periostin-expressing cells in the primary tumor site that promote collagen remodeling and lymphovascular invasion of cancer cells into lymphatic vessels, allowing for their colonization of the sentinel lymph node.
PHD (Doctor of Philosophy)
tumor microenvironment, cancer-associated fibroblasts, lymphovascular invasion, metastatic breast cancer