Abstract B02: Matrix stiffness regulates local metabolism of breast carcinoma cells

Abstract

Abstract Dense breast tissue is one of the single largest risk factors for the development of breast cancer, and one of the primary proteins responsible for increased breast density is the core extracellular matrix (ECM) component, collagen. Similar to other ECM proteins, collagen plays a structural role underlying tissue organization and increased collagen deposition correlates to a stiffer ECM and cellular microenvironment. Interestingly, changes to the stiffness of the ECM or microenvironment have profound and poorly-understood effects on cell migration, cell proliferation, and cancer progression. Consistent with an expanding role of ECM stiffness in cell signaling, we report that increased matrix stiffness also affects cellular metabolism and respiration. Using specific pharmacological inhibitors and quantitative imaging modalities like fluorescence lifetime microscopy, we are able to show that changes in collagen stiffness can cause a metabolic shift towards a more glycolytic, Warburg-like equilibrium in breast carcinoma cells. Matrix stiffness regulates the expression of several metabolic enzymes, including PDHK-1, which is poised to regulate this shift. Note: This abstract was not presented at the conference. Citation Format: Brian Burkel, Suzanne Ponik, Brett Morris, Kevin Eliceiri, Patricia Keely. Matrix stiffness regulates local metabolism of breast carcinoma cells. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B02. doi:10.1158/1538-7445.CHTME14-B02