Abstract A3: Collagen hydroxylases are essential for breast cancer metastasis

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, found in the majority of breast cancers, is associated with an increased risk of metastasis and 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 identify 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 hydroxylase expression in human breast cancer biopsies and evaluate the novel use of ethyl 3,4-dihydroxybenzoate, a hydroxylase inhibitor, which decreases tumor fibrosis and metastasis in a mouse model of breast cancer. Citation Format: Daniele M. Gilkes, Pallavi Chaturvedi, Carmen Wong, Saumendra Bajpai, Hong Wei, Maimon Hubbi, Denis Wirtz, Gregg Semenza. Collagen hydroxylases are essential for breast cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A3.