Abstract 4024: Understanding the role of mitochondria in the progression from normal fibroblasts to DCIS associated fibroblasts

Abstract

Abstract Background and Purpose: Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer which may progress to invasive breast cancer. Many studies have focused on the epithelial cell mechanisms of progression from normal breast tissue to DCIS. However, in this study we want to study mechanisms of progression in cancer associated fibroblasts from normal breast tissue to DCIS. Loss of caveolin 1 (CAV1) in fibroblasts is a marker of reduced mitochondrial membrane potential and is a prognostic biomarker in ductal carcinoma in situ. High mitochondrial membrane potential in epithelial cells is a crucial determinant of carcinogenesis. Methods: In the study we use MCF10DCIS as a model for DCIS. MCF10DCIS.com (MCF10DCIS) is a clonal breast cancer cell line. The MCF10A, non-tumorigenic epithelial cell line, and human immortalized but non-transformed dermal fibroblasts (BJ1) were used study the difference between non-tumorigenic epithelial cells and DCIS and interactions between these two epithelial cells and fibroblasts. In order to study the interaction between epithelial cells and fibroblasts, we set up a coculture model system comprised both epithelial cells and fibroblasts. Immunofluorescence staining and confocal microscopy were used here to visualize the specific protein expression in different cell types. Results: (1) MCF10DCIS cells in coculture with fibroblasts have increased mitotracker red staining while as fibroblasts have decreased mitotracker staining compared to homotypic culture. However, coculture of MCF10A cells with fibroblasts did not change the mitotracker staining in either MCF10A or fibroblasts. (2) Loss of stromal CAV1 protein expression is observed in fibroblasts when fibroblasts are cocultured with MCF10DCIS cells compared to homotypic culture. CAV1 protein expression is unchanged in coculture with MCF10A cells. Conclusion: Previous studies have demonstrated that loss of stromal CAV1 and changes in mitochondrial membrane potential are factors involved in the transition from DCIS to invasive breast cancer. In this study we show that loss of stromal CAV1 and increases in epithelial mitochondrial membrane potential may play a role in the progression to DCIS. Citation Format: Ying-Hui Ko, Zhao Lin, Ubaldo E. Martinez Outschoorn. Understanding the role of mitochondria in the progression from normal fibroblasts to DCIS associated fibroblasts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4024. doi:10.1158/1538-7445.AM2015-4024