title: The role of reactive oxygen species and metabolism on cancer cells and their microenvironment.
abstract: Compelling evidence show that reactive oxygen species (ROS) levels are finely regulated in the cell and can act as "second messengers" in response to diverse stimuli. In tumor epithelial cells, ROS accumulate abnormally and induce signaling cascades that mediate the oncogenic phenotype. In addition to their impact on tumor epithelial cells, ROS also affect the surrounding cells that constitute the tumor microenvironment. Indeed, ROS production increases tumor angiogenesis, drives the onset of inflammation and promotes conversion of fibroblast into myofibroblasts. These cells, initially identified upon wound healing, exhibit similar properties to those observed in fibroblasts associated with aggressive adenocarcinomas. Indeed, analyses of tumors with distinct severity revealed the existence of multiple distinct co-existing subtypes of carcinoma-associated fibroblasts (CAFs), with specific marker protein profiling. Chronic oxidative stress deeply modifies the proportion of these different fibroblast subtypes, further supporting tumor growth and metastatic dissemination. At last, ROS have been implicated in the metabolic reprogramming of both cancer cells and CAFs, allowing an adaptation to oxidative stress that ultimately promotes tumorigenesis and chemoresistance. In this review, we discuss the role of ROS in cancer cells and CAFs and their impact on tumor initiation, progression, and metastasis.
authors.affiliation: Stress and Cancer Laboratory, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, Paris France; Inserm, U830, Paris, F-75248, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Costa
authors.affiliation: Stress and Cancer Laboratory, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, Paris France; Inserm, U830, Paris, F-75248, France.
authors.forename: Alix
authors.initials: A
authors.lastname: Scholer-Dahirel
authors.affiliation: Stress and Cancer Laboratory, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, Paris France; Inserm, U830, Paris, F-75248, France. Electronic address: fatima.mechta-grigoriou@curie.fr.
authors.forename: Fatima
authors.initials: F
authors.lastname: Mechta-Grigoriou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D017382:Reactive Oxygen Species
keywords: Actin; CAF heterogeneity; Caveolin; Mitochondria; Myofibroblast; Oxidative stress; PDGFR; ROS; Stroma