Abstract
Abstract Early metastatic events are often responsible for the recurrence and lethality of prostate cancer. The most frequent site of metastasis is the bone marrow, where small populations of disseminated tumor cells (DTCs) preferentially take residence in the hematopoietic stem cell (HSC) niche. These micro-metastases may survive in a benign, dormant state for years before they become “reawakened” to form full metastases, and are thus difficult to detect and treat. It is unknown what induces and maintains DTC dormancy, and it remains a key question with regard to metastatic prostate cancer treatment and prevention strategies. An essential component of the HSC niche is the osteoblast population to which DTCs bind for support and uptake of secreted factors. We have previously shown that dormant DTCs in the HSC niche display high levels of the receptor tyrosine kinase Axl, and are bound to osteoblasts that secrete its ligand, Gas6. The requirement of Gas6/Axl in DTC dormancy is striking in vivo, but in vitro is not replicable. Addition of Gas6 to prostate cancer cells expressing Axl does not have a significant inhibitory effect on cell proliferation, suggesting the cooperation with other niche factors absent in culture. As the elements of the DTC niche are still being actively explored, this study further supports the complex nature of the mechanisms governing DTC dormancy and preferential survival in the bone marrow niche. Selective targeting of these elements may allow for long term maintenance of the benign, dormant state of DTCs, or coerced reawakening to a more chemotherapy-sensitive state. Citation Format: Haley Axelrod, Kenneth J. Pienta. Gas6/Axl mediation of prostate cancer cell dormancy requires cooperation with additional bone marrow niche components. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 983. doi:10.1158/1538-7445.AM2015-983
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