Cancer metabolism, stemness and tumor recurrence

• DOI: 10.4161/cc.24092
• Publication Date: 2013-05-02T05:04:45Z
• Authors: Joseph M. Curry; Madalina Tuluc; Diana Whitaker-Me...; Julie A. Ames; Archana Anantharaman; Aileen Butera; Benjamin Leiby; David Cognetti; Federica Sotgia; Michael P. Lisanti; Ubaldo E. Martine...
• Keywords: Male; Monocarboxylic Acid Transporters; Monocarboxylate transporters (MCT); Tumor recurrence; MCT4; TOMM20; MCT1; Stem cells; Kaplan-Meier Estimate; Ketone Bodies; 03 medical and health sciences; Report; Mitochondrial Precursor Protein Import Complex Proteins; Biomarkers, Tumor; Humans; Tumor stroma; Lactic Acid; Head and neck cancer; Aged; Cell Proliferation; Aged, 80 and over; 0303 health sciences; Metabolic symbiosis; Membrane Transport Proteins; Cell Differentiation; Epithelial Cells; Fibroblasts; Middle Aged; OXPHOS; 3. Good health; Mitochondria; Oxidative stress; Head and Neck Neoplasms; Female; Glycolysis

Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed determine the state proliferative cells. Interestingly, cell proliferation cells, as marked by Ki-67 immunostaining, strictly correlated with oxidative mitochondrial metabolism (OXPHOS) uptake fuels, detected via MCT1 expression (p < 0.001). More specifically, three tumor were delineated: (1) mitochondrial-rich cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative mitochondrial-poor (Ki-67−/TOMM20−/COX−/MCT1−); (3) stromal (Ki-67−/TOMM20−/COX−/MCT1−). In addition, high stress (MCT4+) very specific for tissues. Thus, next evaluated prognostic value MCT4 a second independent patient cohort 40). Most importantly, non-proliferating epithelial predicted poor clinical outcome (tumor recurrence; p 0.0001; log-rank test), functionally associated FDG-PET avidity 0.04). Similarly, specifically higher stage 0.03), highly marker cancer-associated fibroblasts We propose that is key hallmark tissues drives high-energy adjacent proliferating paracrine transfer fuels (such L-lactate ketone bodies). New antioxidants inhibitors should be developed metabolically target "three-compartment metabolism" cancers. It remarkable two "non-proliferating" populations (Ki-67−/MCT4+) within can actually outcome, likely providing "fuels" burn. Finally, also show normal mucosal tissue, basal "stem cell" layer hyper-proliferative (Ki-67+), (TOMM20+/COX+) programmed use (MCT1+), such bodies L-lactate. common feature both stem As such, consider treating patients Metformin), and/or combination inhibitors, "metabolic symbiosis."