|Education||BS, University of California Irvine|
During prostate tumor development, cancer cells disseminate and preferentially home to the hematopoietic stem cell niche in the bone marrow where they bind to osteoblasts. There, disseminated tumor cells (DTCs) can undergo a period of dormancy for years or decades before re-entering the cell cycle, resulting in clinical recurrence for the patient. Historically, it is understood that the microenvironment of the secondary metastatic site plays a large role in controlling the growth of disseminated cells. Our group has previously shown that the presence of Gas6, a factor secreted by osteoblasts, restricts the growth of prostate cancer (PCa) DTCs in an osseous environment. Gas6 is a ligand for the receptor tyrosine kinases Axl, Tyro3, and Mer. Our group has found that Axl expression is associated with dormant PCa DTCs compared to proliferating metastases. My project utilizes mouse models of metastasis and in vitro coculture models to study how Gas6/Axl is involved in mediating PCa dormancy in the bone marrow microenvironment. Understanding the factor(s) that initiate DTC dormancy in the bone marrow may lead to new therapies aimed at preventing the re-awakening of DTCs responsible for lethal macrometastatic outgrowth.
Axelrod, H. & Pienta, K.J. Axl as a mediator of cellular growth and survival. Oncotarget 5, 8818-8852 (2014). PMID 25344858.