Abstract
Abstract Pre-clinical drug screens, involving culturing well-annotated cancer cell lines on two-dimensional (2D) tissue culture plastic, poorly recapitulate in vivo tumor characteristics and yield candidate drugs which fail clinical trials. We created a multi-layer, hyaluronic acid (HA)-based hydrogel system that incorporates three layers: an acellular cushion layer; an encapsulated cancer cell layer for growth in three dimensions (3D); and a collagen-containing layer that supports the growth of stromal cells on top of the hydrogel (2.5D). Utilizing high-throughput robotic delivery coupled with automated advanced imaging, this formulation provides a highly reproducible system for spheroid culture of prostate (C4-2B) or endometrial (Ishikawa) cancer cell lines in mono- or co-culture with matched stromal cells (HS27a or ESS-1, respectively). Both culture systems provided high cancer cell viability over one week of culture. Cells were treated with drugs from a panel of chemotherapeutic compounds. Cells cultured in our 3D multi-layer HA-based system responded to cytotoxic drugs distinctly from cells grown in 2D and 3D-aliginate, and better predicted the efficacy of chemotherapeutics in clinical trials. We have also successfully incorporated cells derived from patient derived xenograft (PDX) models in our 3D culture system. Wider adoption of 3D automated screening has the potential to speed drug discovery and increase success of drugs in clinical trials. Citation Format: Pamela E. Constantinou, Brian J. Engel, Lindsey K. Sablatura, Nathaniel J. Doty, Daniel D. Carson, Mary C. Farach-Carson, Daniel A. Harrington, Thomas I. Zarembinski. A multi-layered, hydrogel system for automated 3D high throughput drug screening of cancer-stromal cell co-cultures. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 604.
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