Work

Characterization of the effects of defined, multidimensional culture conditions on conditionally reprogrammed primary human prostate cells

Year: 2017

Type: article

Abstract: // Lucas Tricoli 1, 4 , Aisha Naeem 1 , Erika Parasido 1 , John P. Mikhaiel 1 , Muhammad Umer Choudhry 1 , Deborah L. Berry 1 , Iman A. Abdelgawad 2 , Richard J. Lee 3 , Adam S. Feldman 3 , Chukwuemeka Ihemelandu 1 , Maria Avantaggiati 1 , Deepak Kumar 4 , Stephen Byers 1 , Rosa Gallagher 5 , Julia Wulfkuhle 5 , Emanuel Petricoin 5 , Olga Rodriguez 1, 6 and Chris Albanese 1, 6 1 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA 2 National Cancer Institute of Egypt, Cairo, Egypt 3 Massachusetts General Hospital Cancer Center, Boston, MA, USA 4 Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC, USA 5 Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA 6 Preclinical Imaging Research Laboratory, Georgetown University Medical Center, Washington, DC, USA Correspondence to: Chris Albanese, email: [email protected] Keywords: prostate; cancer; primary tissue; reprogrammed cells; androgen Received: October 26, 2017 Accepted: November 02, 2017 Published: December 18, 2017 ABSTRACT The inability to propagate human prostate epithelial cells indefinitely has historically presented a serious impediment to prostate cancer research. The conditionally reprogrammed cell (CRC) approach uses the combination of irradiated J2 mouse fibroblasts and a Rho kinase inhibitor such as Y27632 to support the continuous culture of cells derived from most epithelial tissues, including the prostate. Due to their rapid establishment and overall ease of use, CRCs are now widely used in a variety of basic and preclinical settings. In addition, CRCs were successfully used to clinically treat respiratory papillomatosis. Although both normal and tumor-derived prostate CRCs have been used to study the basic biology of prostate cancer and to test new therapies, certain limitations exist. We have previously reported that prostate CRCs form functional prostate glands when implanted under the mouse renal capsule. However in conventional culture, the prostate CRCs exist in an adult stem-like, transient amplifying state and consequently do not adequately recapitulate several important features of a differentiated prostate epithelium. To address these limitations, we previously described a transwell dish-based model that supported the culturing of prostate CRCs and the collection of cells and cell extracts for molecular and genetic analyses. Using normal and tumor-derived prostate CRCs, we describe the combined effects of the multi-dimensional transwell platform and defined culture media on prostate cellular proliferation, differentiation and signaling.

Source: Oncotarget

DOI: 10.18632/oncotarget.23363