Abstract 5106: Unexpected roles for stromal MMP3 during breast cancer

Abstract

Abstract Matrix metalloproteinases (MMPs) are a family of proteases that have been shown to contribute to the degradation of components of the extracellular matrix and other substrates to promote cancer progression and metastasis. Stromelysin / matrix metalloproteinase-3 (MMP3) is one member of the matrix metalloproteinase family that is overexpressed in human breast cancer. During breast cancer, MMP3 is expressed primarily by stromal cells but also by cancer cells. Overexpression of MMP3 induces an epithelial-to-mesenchymal transition (EMT), promotes hyperplastic growth, and expands a mammary gland stem cell population. In addition, MMP3 is required for the mammary gland stem cell population. In this study, we determined if stromal MMP-3 is required for breast cancer progression for primary and metastatic lung tumor growth. To study this, we transplanted mammary epithelial cancer cells (V0PyMT) into the mammary glands of MMP3 knockout and heterozygous syngeneic mice. We quantified the tumor burden of both primary and metastastic tumors over time and discovered that elimination of stromal MMP3 increased the tumor burden. The tumor pathologies, proliferation rate, and apoptosis were similar between cancer and not cancer tissue. In contrast, the vasculature density decreased. These data suggest that stromal MMP3 inhibits, but is not required for, the development of the primary breast tumor. However, in contrast to our primary tumor data, we interestingly discovered that stromal MMP3 was required for visible lung metastases. These experiments begin to distinguish between the contrasting roles of stromal and epithelial MMP3 during breast cancer. Our data reveal that MMP3 contributes to the metastatic tumor formation within the lungs. This study will help to elucidate new mechanisms through which MMP3 functions within particular microenvironmental contexts during breast cancer progression. Citation Format: Emilia Hartland, Charley Jang, Ricardo Romero Moreno, Megan McGarel, Sunil Badve, Laurie Littlepage. Unexpected roles for stromal MMP3 during breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5106.