2. Lactic acid-mediated tumor progression. The accumulationof an enzyme facilitates the high conversion rateof pyruvate to lactate, and LDH-A has been observed to becritical in the development and progression of cancer. Followingproduction, lactate is transported out of the cancercell and across the plasma membrane by monocarboxylatetransporter (MCT) family proteins. MCTs are proton-linkedtransporters and are involved primarily in the transport ofmonocarboxylic acids. MCT 1, an import transporter, is utilizedin oxidative tumors to shuttle exogenous lactate as anenergy source. The shuttling of lactate by MCT 1 into endothelialcells drives the CXCL8 pathway, enabling endothelialcell migration to stimulate angiogenesis. Lactate alsodrives the process of angiogenesis by promoting the productionof VEGF (78). Furthermore, MCT1 shuttling of lactatestimulates IL-8 mRNA expression in endothelial cells,a finding that is also important for angiogenesis (79). Inaddition, MCT4 releases lactate from glycolytic tumors (80).Overall, as a common feature of malignant cells, increasedglucose uptake and lactate production, even under normoxicconditions, is involved in cancer survival and proliferationvia several mechanisms, including evading theimmune system and modulating cell motility. Furthermore,the accumulation of lactate in cancer has been demonstratedto possess clinical relevance as a prognostic marker(81).