Abstract P6-02-07: In vitro 3D Model of Breast Tumor Stroma

Abstract

Abstract One in eight women is diagnosed with breast cancer in the United States every year. Despite advancements for early diagnosis and initial treatment of breast cancer, the complexity and multiplicity of biological factors and barriers in tumor microenvironment prevent potent active agents from reaching their targets in cancer cells. There has been a growing body of evidence about the importance of three-dimensional (3D) culture systems in discovery and modeling of biological processes with in vivo relevance. A few examples that have been reported in 3D monocultures include different growth patterns of normal and malignant breast cancer cells in 3D cultures of laminin-rich gels and effect on cell polarity pathways. These effects are not observed in conventional two-dimensional (2D) cultures, showing that cells organized in a 3D matrix can shed light on novel mechanisms in breast cancer biology. Moreover, neither 2D nor 3D monoculture models available today mimic the complexity of clinically observed tumor microenvironment (tumor stroma), which also contains fibroblasts, macrophages and endothelial cells and represents an important physiological barrier for efficient delivery of therapeutics to breast tumors. In this work we propose and investigate an in vitro system mimicking the tumor microenvironment in which relevant cell populations in tumor microenvironment are co-cultured with breast cancer cells*. The system uses the Nano3D® platform based on magnetic levitation. 3D tumor models for breast cancer were designed and optimized by co-culturing SUM159 and MDA-MB-231, triple negative breast cancer cells, with 293T fibroblasts. The cells were co-cultured at different ratios and for a various time periods. Further, to assess the similarity of the in vitro system to the in vivo disease, we tested an an orthotopic model of breast cancer in SCID beige mice. Histological analysis of frozen tissues from in vitro and in vivo studies confirmed that the in vitro 3D system based on the mixture of fibroblasts and cancer cells has structural similarities to the in vivo observed tumor stroma. Engineering an in vitro 3D tumor model that accurately represents the in vivo tumor will further benefit research efforts in breast cancer diagnosis and therapy. *Patent pending – inventors: B. Godin, G. Souza, and B. Dave Acknowledgments: The authors acknowledge a financial support from the Susan G. Komen Postdoctoral Fellowship #PDF12229449. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-02-07.