Abstract IA26: Conditionally Reprogrammed Cells (CRCs): A simple, two-component cell system for basic and clinical cancer research

Abstract

Abstract Conditional reprogramming (CR) is a new cell biology technique that allows for the rapid and efficient outgrowth of matched normal and tumor epithelial tissue from patient samples. This approach combines the use of a ROCK inhibitor and irradiated feeder cells to induce and select for stem-like cells from adult tissues. While normal CR cells can be maintained for prolonged periods in vitro (in most cases they are conditionally immortalized), they retain their potential to differentiate normally when returned to an appropriate in vivo or in vitro environmental niche. Tumor cells can also be readily established in culture, although they can exhibit reduced dependence upon feeder cells and ROCK inhibitor for continued proliferation. The high efficiency of this system makes it feasible to establish cell cultures from rare tumor specimens. Minor modifications of the CR method also allow for the outgrowth of neuroendocrine and mesenchyme-like cells, possibly including cells that have undergone epithelial/mesenchymal transition. Biobanking using the CR method is now standardly applied in our pathology department in order to generate a renewable resource of patient samples for scientific investigation. The greatest challenge for routine application of this method is the selection of tumor cells from surgical biopsy specimens. Since both normal and tumor cells proliferate under these conditions, it is critical to evaluate the histologic composition of the biopsies and to validate the outgrowth of tumor cells using molecular biomarkers. Modified growth conditions are being developed to facilitate the selective outgrowth of tumor cells from mixed normal/tumor samples. This cell culture system has been used to identify new therapies for rare tumors (1) and characterize patient biopsies (2), and is now being applied broadly in new NCI initiatives for second-generation cancer cell models. 1. N Engl J Med 367:1220, 2012 2. Science 346:1480, 2014 Citation Format: Richard Schlegel. Conditionally Reprogrammed Cells (CRCs): A simple, two-component cell system for basic and clinical cancer research. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA26.