Abstract 3937: Collagen prolyl hydroxylases are essential for breast cancer metastasis.

Abstract

Abstract Metastasis is the leading cause of death among patients who have breast cancer. Understanding the role of the extracellular matrix in the metastatic process may lead to the development of improved therapies to treat cancer patients. Intratumoral hypoxia is found in the majority of breast cancers and is associated with an increased risk of metastasis and patient mortality. Here we demonstrate that hypoxia-inducible factor 1 activates the transcription of genes encoding collagen prolyl hydroxylases that are critical for collagen deposition by breast cancer cells. We show that expression of collagen prolyl hydroxylases promotes cancer cell alignment along collagen fibers, resulting in enhanced cancer cell invasion and metastasis to lymph nodes and lungs. We establish the prognostic significance of collagen prolyl hydroxylase mRNA expression in human breast cancer biopsies and evaluate the novel use of ethyl 3,4-dihydroxybenzoate, a prolyl hydroxylase inhibitor, which decreases tumor fibrosis and metastasis in a mouse model of breast cancer. Citation Format: Daniele M. Gilkes, Pallavi Chaturvedi, Saumendra Bajpai, Maimon Hubbi, Denis Wirtz, Gregg Semenza. Collagen prolyl hydroxylases are essential for breast cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3937. doi:10.1158/1538-7445.AM2013-3937