Abstract 322: A uniqueex vivotumor model: 3D co-cultured system with cancer cells and stromal tissue for drug evaluation

Background;Recently, three-dimensional culture model has been reported as better tumor model than 2D culture. The importance of interaction between cancer and stromal cells has been widely recognized in tumor progression and resistance against treatment. So that ex vivo model which recaptures the tumor microenvironment is required to perform drug evaluation mimicking the patient tumor tissue. Methods; Layered 3D stromal tissues with microvascular network were produced by culturing normal fibroblasts and endothelial cells coated with the extra-cellular matrix (ECM) and natural polysaccharide, namely collagen and heparin. The layered 3D stromal tissues and co-cultured tumor were morphologically evaluated by HE staining, immunohistochemistry and immunofluorescence (IF). Drug sensitivity assay were conducted using popular colorectal cancer cell lines, and patient-derived cell lines (PDCs) established in JFCR under approved IRB. Remaining cancer cells post drug treatment were quantified by IF and imaging analysis. Furthermore, in vivo drug sensitivity was also evaluated. Results: The CD31 positive luminal structures which shows vascular endothelial tube formation were observed intra multi-layered tissues. The dense microvascular network tended to be formed nearby cancer cells. In comparison with 2D culture model, decreased drug sensitivities were represented in the layered 3D co-cultured model. The evaluated drug sensitivities in 3D model may reflect the response of cancer cells in in vivo. Conclusion; We developed the layered 3D stromal tissue culture system including blood micro-vessels. Our unique 3D ex vivo model appear to be a valuable tool for drug evaluation, and thus further studies are underway to confirm the usefulness of our model. Testing approved and/or developing compounds with PDCs in the model would potentially enable better prediction their efficacy. Citation Format: Yuki Takahashi, Kei Tsukamoto, Yuki Shimizu, Ryohei Katayama, Eiji Shinozaki, Satoshi Nagayama, Michiya Matsusaki, Shiro Kitano, Kensei Yamaguchi, Naoya Fujita. A unique ex vivo tumor model: 3D co-cultured system with cancer cells and stromal tissue for drug evaluation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 322.