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Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness
INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915¸13288 Marseille cedex 9, France
* Author to whom correspondence should be addressed.
Received: 1 November 2010; in revised form: 7 December 2010 / Accepted: 13 December 2010 / Published: 16 December 2010
Abstract: Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.
Keywords: pancreatic cancer; hypoxia; metabolism; cachexia
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Vasseur, S.; Tomasini, R.; Tournaire, R.; Iovanna, J.L. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness. Cancers 2010, 2, 2138-2152.
Vasseur S, Tomasini R, Tournaire R, Iovanna JL. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness. Cancers. 2010; 2(4):2138-2152.
Vasseur, Sophie; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. 2010. "Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness." Cancers 2, no. 4: 2138-2152.