Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis
2015 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 36, S184-S202 p.Article, review/survey (Refereed) Published
Angiogenesis is an important hallmark of cancer. We reviewed the various pathways controlling angiogenesis, summarized the possible role of specific environmental chemicals disrupting these pathways and listed assays for assessing the effects of low-dose exposures to chemicals in promoting tumor angiogenesis.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.
Place, publisher, year, edition, pages
Oxford University Press (OUP): Policy B - Oxford Open Option B , 2015. Vol. 36, S184-S202 p.
IdentifiersURN: urn:nbn:se:liu:diva-120285DOI: 10.1093/carcin/bgv036ISI: 000357048100010PubMedID: 26106137OAI: oai:DiVA.org:liu-120285DiVA: diva2:843014
Funding Agencies|Ohio State University College of Medicine; The OSU James Comprehensive Cancer Center (OSUCCC); OSUCCC Translational Therapeutics Program; Ministry of Science and Technology of Taiwan [NSC93-2314-B-320-006, NSC94-2314-B-320-002]; Taipei Medical University [TMU101-AE3-Y19]; INSERM; University of Strasbourg, France; Fondazione Cariplo [2011-0370]; Kuwait Institute for the Advancement of Sciences [2011-1302-06]; Grant University Scheme (RUGS) Ministry Of Education Malaysia [04-02-12-2099RU]; Italian Ministry of University and Research [2009FZZ4XM_002]; University of Florence; US Public Health Service [RO1 CA92306, RO1 CA92306-51, RO1 CA113447]; Department of Science and Technology, Government of India [SR/FT/LS-063/2008]; NIEHS [N01-ES 35504, HHSN27320140003C]2015-07-242015-07-242016-04-24