Abstract
Abstract Prostate cancer is the most prevalent and the leading cause of cancer-related death among men, particularly African Americans. The cellular and molecular mechanisms contributing to this deadly disease remain largely unknown. As such, there are no effective strategies to treat metastatic cancer and improve patient outcomes. Anchorage-independent growth of circulating prostate tumor cell clusters is essential for developing cancer metastasis. However, there is no model system to study the molecular and functional characteristics of prostate tumor cell clusters reminiscent of the bloodstream in a laboratory setting. In addressing this need, we have established nonadherent LNCaP cell clusters, LN-G2 and LN-G3, under androgen-depleted growth conditions in a simulated microgravity bioreactor called Slow Turning Lateral Vessel (STLV). Our quantitative PCR analysis repeatedly demonstrated that LN-G2 and LN-G3 cell populations expressed high levels of the well-characterized CD44 and CXCR4 cancer stem cell maker, respectively, compared to the LNCaP parental. In addition, our functional analysis indicates that, unlike the LNCaP cell, LN-G2 and LN-G3 cells showed superior clonogenic and growth behaviors in response to androgen depletion and enzalutamide-treatment under adherent monolayer and nonadherent conditions. These observations suggest that cancer stem cell-like cell clusters that survived under microgravitational stress confer distinctive molecular and functional properties associated with superior survival and contribute to castration-resistant prostate cancer. Furthermore, the STLV bioreactor could help enrich cancer stem cell populations and enhance our understanding of the underlying mechanisms of lethal cancer, which may lead to novel therapeutics to improve patient outcomes. Citation Format: Kezhan Khazaw, Sebnem Unlu, Abdulrahman M. Dwead, Bekir Cinar. Enrichment of nonadherent prostate cancer stem cell populations using simulated microgravity bioreactor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4303.
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