• 1 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • 2 INSERM U1113, team 3 "Cell Signalling and Communication in Kidney and Prostate Cancer", University of Strasbourg, Facultée de Médecine, 67085 Strasbourg, France, Department of Cell and Developmental Biology, University of California, Irvine, CA 92697, USA
  • 3 National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-3375, USA
  • 4 Department of Life Sciences, Tzu-Chi University, Taiwan, Republic of China
  • 5 Department of Microbiology and Immunology, Taipei Medical University, Taiwan, Republic of China
  • 6 INSERM U1113, team 3 "Cell Signalling and Communication in Kidney and Prostate Cancer", University of Strasbourg, Facultée de Médecine, 67085 Strasbourg, France
  • 7 Department of Pathology, Kuwait University, Safat 13110, Kuwait
  • 8 Department of Experimental and Clinical Medicine, University of Firenze, Florence 50134, Italy
  • 9 Department of Environmental and Radiological Health Sciences , Colorado State University/Colorado School of Public Health, Fort Collins, CO 80523, USA
  • 10 Environmental and Molecular Toxicology, Environmental Health Science Center, Oregon State University, Corvallis, OR 97331, USA
  • 11 Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, Bologna, Italy
  • 12 Faculty of Medicine and Health Sciences, University Putra, Serdang, Selangor, Malaysia
  • 13 Institute of Molecular Genetics, National Research Council, Pavia 27100, Italy
  • 14 Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate , Health Products and Food Branch Health Canada, Ottawa, Ontario K1A0K9, Canada
  • 15 Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC 20057, USA
  • 16 Advanced Molecular Science Research Centre (Centre for Advance Research), King George's Medical University, Lucknow, Uttar Pradesh 226003, India
  • 17 Mediterranean Institute of Oncology, Viagrande 95029, Italy
  • 18 Urology Department, kasr Al-Ainy School of Medicine, Cairo University, El Manial, Cairo 12515, Egypt
  • 19 Getting to Know Cancer, Truro, Nova Scotia B2N 1X5, Canada
  • 20 Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden and
  • 21 Integrated Laboratory Systems, Inc., in support of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, NIEHS, MD K2-16, RTP, NC 27709, USA
Carcinogenesis, 2015 Jun;36 Suppl 1:S184-202.
PMID: 26106137 DOI: 10.1093/carcin/bgv036


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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.