Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis
Year: 2015
Type: review
Abstract: One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.
Source: Carcinogenesis
Authors: Zhiwei Hu, Samira A. Brooks, Valérian Dormoy, Chia-Wen Hsu, Hsue-Yin Hsu, Liang-Tzung Lin, Thierry Massfelder, W.Kimryn Rathmell, Menghang Xia, Fahd Al-Mulla, Rabeah Al-Temaimi, Amedeo Amedei, Dustin G. Brown, Kalan R. Prudhomme, Anna Maria Colacci, Roslida A. Hamid, Chiara Mondello, Jayadev Raju, Elizabeth P. Ryan, Jordan Woodrick, A.Ivana Scovassi, Neetu Singh, Monica Vaccari, Rabindra Roy, Stefano Forte, Lorenzo Memeo, Hosni K. Salem, Leroy Lowe, Lasse Jensen, William H. Bisson, Nicole Kleinstreuer
Institutions: University of North Carolina at Chapel Hill, National Institutes of Health, Inserm, University of California, Irvine, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, UNC Lineberger Comprehensive Cancer Center, Taipei Medical University, The Ohio State University, Université de Strasbourg, National Center for Advancing Translational Sciences, Tzu Chi University, Kuwait University, University of Florence, Colorado School of Public Health, Colorado State University, Oregon State University, Universiti Putra Malaysia, Istituto di Genetica Molecolare, National Research Council, Health Canada, Georgetown University, Georgetown University Medical Center, Georgetown Lombardi Comprehensive Cancer Center, King George's Medical University, Cairo University, Cairo University hospitals, Linköping University, National Institute of Environmental Health Sciences, Integrated Laboratory Systems, Inc.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: Ohio State University, Institut National de la Santé et de la Recherche Médicale, National Science Council, Fondazione Cariplo, Université de Strasbourg, Università degli Studi di Firenze, Ministry of Science and Technology, Taiwan, Taipei Medical University, National Institutes of Health, U.S. Public Health Service, National Cancer Institute, National Institute of Environmental Health Sciences
Awards: G1327623919, DNA Repair of Endogenous Lesions in Carcinogenesis, The Halifax Project: Chemical Mixtures and Cancer, G1756123706, Regulations of DNA Alkylation/Deamination Damage Repair, SUPPORT CONTRACT FOR THE NTP INTERAGENCY CENTER/VALIDATION OF ALT METHODS, G5944248625, G6494616852, G7214565560, Optofluidic chips for the study of cancer cell mechanical properties and invasive capacities, G7971958640, G8725524060, Cancer Center Support Grant, Training Grant In Tumor Biology
OpenAlex ID: W2134835775