Harrell Lab Research
Identification of genetic mediators of breast cancer liver metastasis, METAvivor
Dr. Harrell's lab studies mechanisms that contribute to breast cancer metastasis. There are at least five genetically distinct types of human breast cancers and each intrinsic subtype exhibits a different predilection to metastasize to specific vital organs. Triple negative breast cancers (ER-/PR-/HER2-), which includes the Basal-like and Claudin-low subtypes, most aggressively metastasize to the brain and lung, whereas HER2-Enriched preferentially metastasize to the liver, and the estrogen-sensitive Luminal A and Luminal B tumors most readily spread to the bone. Understanding the mechanisms that drive these fundamental differences in metastagenicity is a major focus of the lab.
Since Triple Negative tumors are often identified at diagnosis, or shortly thereafter, and have limited therapeutic options, we have been developing models to study this process.In vitro co-culture models have identified that Claudin-low cancer cells can physically interdigitate with blood and lymphatic vascular endothelial cells, creating a cancer-vascular mosaic vessel, which facilitates cancer entry into the bloodstream. To reduce intravasation, current research projects are aimed inhibiting this interaction. To understand the pathways that promote extravasation of cancer cells into vital organs, we are utilizing patient-derived xenograft (PDX) models. Unlike cell lines, which have been selected to grow on plastic tissue culture dishes, PDX models retain their genetic and metastatic characteristics. By labeling these cells with fluorescent or luciferase markers, we have been able to isolate metastases and identify genes that promote growth in the liver, lung, and brain. We are now targeting these genes to inhibit metastatic growth.