title: Cycling hypoxia: A key feature of the tumor microenvironment.
abstract: A compelling body of evidence indicates that most human solid tumors contain hypoxic areas. Hypoxia is the consequence not only of the chaotic proliferation of cancer cells that places them at distance from the nearest capillary but also of the abnormal structure of the new vasculature network resulting in transient blood flow. Hence two types of hypoxia are observed in tumors: chronic and cycling (intermittent) hypoxia. Most of the current work aims at understanding the role of chronic hypoxia in tumor growth, response to treatment and metastasis. Only recently, cycling hypoxia, with spatial and temporal fluctuations in oxygen levels, has emerged as another key feature of the tumor environment that triggers different responses in comparison to chronic hypoxia. Either type of hypoxia is associated with distinct effects not only in cancer cells but also in stromal cells. In particular, cycling hypoxia has been demonstrated to favor, to a higher extent than chronic hypoxia, angiogenesis, resistance to anti-cancer treatments, intratumoral inflammation and tumor metastasis. These review details these effects as well as the signaling pathway it triggers to switch on specific transcriptomic programs. Understanding the signaling pathways through which cycling hypoxia induces these processes that support the development of an aggressive cancer could convey to the emergence of promising new cancer treatments.
authors.affiliation: URBC-NARILIS, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium. Electronic address: carine.michiels@unamur.be.
authors.forename: Carine
authors.initials: C
authors.lastname: Michiels
authors.affiliation: URBC-NARILIS, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Tellier
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, 53 Avenue Mounier, B1.53.09, B-1200 Brussels, Belgium. Electronic address: olivier.feron@uclouvain.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D010100:Oxygen
keywords: Angiogenesis; Cancer microenvironment; Cycling/intermittent hypoxia; Inflammation; ROS production; Transcriptional response