Abstract 4829: Development of rapid 3-dimensional culture conditions that support the in vitro differentiation of conditionally reprogrammed primary prostate cells for the study of prostate cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.4829-4829
• Main Authors: Tricoli, Lucas James, Berry, Deborah, Parasido, Erika, Naeem, Aisha, Rodriguez, Olga, Abdelgawad, Iman, Lee, Richard, Feldman, Adam, Albanese, Chris
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-4829

Despite decades of research into the causes and possible cures, prostate cancer (PCa) remains the second leading cause of cancer related death in men with over 26,000 deaths each year in the United States alone. While many of the studies performed over the years have identified important genes and signaling pathways that are involved in prostate carcinogenesis, the fact remains that due to the limited and suboptimal prostate cell lines available for correlative analyses, significant unmet needs exist in validating clinical findings. With this realization, many agencies such as the DOD and the NIH are funding more rapid and clinically relevant patient derived models to fill a void in our understanding of, and our ability to treat, cancer. Our research has been on the forefront in development of a novel approach to use patient samples for basic, preclinical and clinical applications, significantly advancing personalized medicine with a revolutionary new primary cell culture technique termed conditionally reprogrammed cells (CRCs). In fact, the CRC approach is a major focus area of NIH U01/PAR 16-344. We have pioneered the CRC technology for the rapid establishment and expansion of patient-derived normal and cancerous prostate cell lines in typical tissue culture conditions. We hypothesize that improved in vitro and in vivo platforms using patient-derived prostate cells (e.g. CRCs) are required for the elucidation and subsequent experimental verification of key molecular and genetic drivers for PCa as well as better curative approaches. While prostate CRCs retain their lineage commitment, they fail to express many of the differentiation markers associated with luminal prostate cells when grown under normal two dimensional (2D) culture conditions. We have therefore established three dimensional (3D) non-spheroid based platforms for differentiation of both normal and malignant prostate CRCs. These include both transwell-based systems and decellularized tissue matrices that use defined differentiation medias to enable AR activation and a luminal cell phenotype. We have now demonstrated the in vitro re-engagement of key determinates in the AR pathway and differentiation to luminal prostate cells. Documentation of the proper engagement of AR signaling is a significant step in developing a more accurate and tractable model for prostate cancer research and distinguishing between indolent and aggressive disease. Citation Format: Lucas James Tricoli, Deborah Berry, Er