Energy metabolism in bone tumors : Fuel selection and adaptation
Résumé
It has long been recognized that cancer cells exhibit altered patterns of metabolism that allow them to meet the biosynthetic demands of rapid proliferation and overcome metabolic stress imposed by the microenvironment. In this chapter, we aim to recapitulate knowledge on energetic metabolism and reprogramming in osteo-oncology. Diagnosis and staging of bone metastases using 18 Fluorine labeled Glucose, choline and folate and emission tomography and computerized tomography (PET/CT) reflect tumor cells energetic metabolism. Metabolites and associated gene regulators involved in bone metastases and/or osteosarcoma progression are also described including, glucose, lactate, amino-acid, cholesterol, fatty acids and derived mitochondrial activity ROS. Moreover several master regulators of energy metabolism in normal physiology, metabolic syndromes and cancer (PPARg, ERRa, PGC1a, CREB, MYC, RAS, EWS-FLI, TMPRSS2-ERG and mTOR) are identified in bone metastases and primary bone tumor. Interestingly, factors that were first detected in bone physiology (RANKL/OPG/RANK, Runx2, OPN, OCN, POSTN and SOST) have been recently identified as regulators of energetic metabolism. Finally, in clinic, treatments targeting metabolism (everolimus, statin,…) have an impact on bone metastases regression, suggesting that targeting energetic metabolism may constitute a new therapeutic pathway in osteo-oncology. Research Highlights: • High diversity of metabolic fuels to feed bone tumor. • Strong energetic metabolism genes program allow tumor cells to survive and progress in bone microenvironment. • Osteomimicry may contribute to bone tumor adaptation to their metabolic environment.
Domaines
Cancer
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