Abstract 3105: Extracellular matrix density and the development of breast acini and ducts in 3D cultures

Abstract

Breast epithelial cells develop into polarized and highly organized acinar and ductal structures in response to stromal cues, including extracellular matrix composition and density, which can in part be reproduced in 3D culture conditions. Here we present the effects of increasing density of stroma composition on the ability of heterotypic cultures of epithelial and mesenchymal stem cells to organize into acinar and tubular structures in in vitro 3D cultures. Normal murine mammary gland (NMuMG) cells were cultured in combination (30:70) with mouse mesenchymal stem cells (D1), in 3D matrices composed of increasing concentrations (0.8 to 8 mg/ml) of collagen I and growth-factor reduced Matrigel® (1:1). The organization of the breast-like structures was assessed by immunohistochemistry. After 3-5 days in culture, the organization and the presence of acinus-like and tubule-like structures were determined. By immunohistochemical analysis, NMuMG cells co-cultured with D1 cells formed acinar and tubular structures with the NMuMG epithelial cells surrounding a lumen composed of dead cells while the D1 cells were mostly peripheral and separated by laminin-positive basement membrane. Collagen I /Matrigel® matrices with density of 1.6 and 2.4 mg/ml were associated with significantly higher concentrations of acinus-like structures compared to other densities (p<0.05). In contrast, the high concentration (8mg/ml) matrix prevented the development of acinus-like structures (p<0.05). The number of tube-like structures was drastically reduced as the density of the collagen I / Matrigel matrix increased from 0.8 to 3.2 mg/ml (p<0.05). These results indicate that the density of the matrix influences the organization and the generation of acinus-like and duct-like structures in the mammary tissues. Whether the biomechanical and density properties of the breast extracellular matrix can be harnessed to build improved tissue culture systems to benefit breast cancer patients remains to be determined. This work was supported by grants from the Department of Defense Era of Hope program (BC044778) and the National Science Foundation EFRI program (CBE0736007). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3105. doi:10.1158/1538-7445.AM2011-3105