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Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis

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https://ir.library.oregonstate.edu/concern/articles/nv935473x

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  • 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.
  • This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Oxford University Press. The published article can be found at: http://carcin.oxfordjournals.org/. The publisher and the author(s) have made this article open access.
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  • Hu, Z., Brooks, S. A., Dormoy, V., Hsu, C. W., Hsu, H. Y., Lin, L. T., ... & Kleinstreuer, N. (2015). Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis. Carcinogenesis, 36(Suppl 1), S184-S202. doi:10.1093/carcin/bgv036
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  • 36
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  • Supp. 1
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  • The Ohio State University College of Medicine, The OSU James Comprehensive Cancer Center (OSUCCC), OSUCCC Translational Therapeutics Program (to Z. H.); Ministry of Science and Technology of Taiwan (NSC93-2314-B-320-006 andNSC94-2314-B-320-002 to H.-Y. H.); Taipei Medical University (TMU101-AE3-Y19 to L.-T. L.); INSERM and University of Strasbourg, France (to T. M.); Fondazione Cariplo (2011-0370 to C.M.); Kuwait Institute for the Advancement of Sciences (2011-1302-06 to F. al-M.); Grant University Scheme (RUGs) Ministry of Education Malaysia (04-02-12-2099RU to R.A.H.); Italian Ministry of University and Research (2009FZZ4XM_002 to A.A); the University of Florence (ex60%2012 to A.A.); US Public Health Service Grants (RO1 CA92306, RO1 CA92306-S1, RO1 CA113447to R.R.); Department of Science and Technology, Government of India (SR/FT/LS-063/2008 to N.S.); NIEHS contracts (N01-ES 35504 and HHSN27320140003C to N.K.). We are also thankful for National Institute of Environmental Health Sciences of USA for travel grant support for team members to attend the Halifax Workshop in August 2013.
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