Abstract 5272: A novel organotypic 3D invasion platform to advance anticancer drug development

Abstract

Abstract Tumor cell invasion is traditionally studied in three-dimensional (3D) organotypic models composed of type I collagen and fibroblasts, where various cell types and the extracellular matrix in the tumor microenvironment (TME) affects tumor cell behavior. As both molecular and cellular components of TME are cardinal participants in tumor progression, special attention should be addressed in the growth environment. As there is urgent need for more predictive models to be utilized in drug discovery and development, organotypic 3D in vitro assay provides an applicable platform. We characterized a novel organotypic model based on human uterine leiomyoma tissue to be used in drug development. To evaluate the general applicability of the myoma model, human tongue squamous cell carcinoma cells (HSC-3) and human triple negative breast cancer cells (MDA-MB-231(SA)-GFP) were cultured on top of human uterine leiomyoma tissue. Organotypic sections were examined by immunohistochemical stainings against cytokeratin and GFP, where invasion area and depth were measured. The organotypic myoma model also gives opportunity for ELISA, RIA and Western blotting analysis of the culture media. The used cell lines were found to invade in highly distinct patterns. This organotypic 3D myoma model provides a potent tool for analyzing the behavior of tumor cells. Moreover, we conclude that established organotypic 3D in vitro platform gives remarkable advantages to screen potential therapeutic options by producing totally new commercially usable models and innovative treatment approaches that target both the cancer cells and the TME components. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5272. doi:1538-7445.AM2012-5272