Abstract 540: Lactate as a mediator of mesenchymal stem cell interactions within the tumor microenvironment

Abstract

Abstract Mesenchymal stem cells (MSCs) are multipotent stromal precursor cells that have the capacity to migrate, proliferate, differentiate and contribute in vivo to the hypoxic tumor stroma. Cancer cells primarily depend on the anaerobic breakdown of glucose to generate ATP, even in the presence of oxygen. A consequence of this altered metabolic phenotype of cancer cells is the accumulation and secretion of lactate. Recent reports suggest that lactate produced by cancer cells may be taken up by stromal cells and recycled to regenerate pyruvate. Interestingly, stromal cells can efflux pyruvate to serve as a power supply to sustain the metabolic needs of cancer cells. Here we provide evidence that MDA-MB-231 and MCF-7 breast cancer cell lines secrete enhanced levels of lactate (2-fold) under hypoxia (1.5% O2) as compared to normoxia (21% O2). Analysis of MSC migration, showed that 15mM lactate enhanced MSC migration over 3-fold compared to control medium. Lactate stimulation of MSCs induced expression of a functional monocarboxylate transporter MCT-1, one of the proteins involved in lactate transport, at both mRNA and protein levels. Furthermore, activation of Stat3 signaling leading to enhanced MSC migration and NF-[[Unable to Display Character: ĸ]]B regulated survival pathways following lactate stimulation was observed suggesting that lactate plays a role in the metabolic fate of cancer cells through the recruitment of MSCs. Delineating the interaction between MSCs, lactate and the tumor microenvironment will be fundamental in understanding tumor cell metabolism and provide knowledge for the development of novel anticancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 540.