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The effect of environmental chemicals on the tumor microenvironment Public Deposited

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  • Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.
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  • Casey, S. C., Vaccari, M., Al-Mulla, F., Al-Temaimi, R., Amedei, A., Barcellos-Hoff, M. H., ... & Felsher, D. W. (2015). The effect of environmental chemicals on the tumor microenvironment. Carcinogenesis, 36(Suppl 1), S160-S183. doi:10.1093/carcin/bgv035
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  • 36
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  • Supp. 1
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  • The authors would like to acknowledge the NIH NationalInstitute of Environmental Health Sciences (R01ES017452)and travel grant support. The authors also acknowledgeFondazione Cariplo (2011-0370 to C.M.), Kuwait Institute forthe Advancement of Sciences (2011-1302-06 to F.Al-M.), GrantUniversity Scheme (RUGs) Ministry of Education Malaysia (04-02-12-2099RU to R.A.H.), Italian Ministry of University andResearch (2009FZZ4XM_002 to A.A.), the University of Florence(ex60%2012 to A.A.), US Public Health Service Grants (RO1CA92306, RO1 CA92306-S1, RO1 CA113447 to R.R.), Departmentof Science and Technology, Government of India (SR/FT/LS-063/2008 to N.S.), a grant from the National Cancer Institute(R01CA552679 to S.R.), the Miguel Servet Program (CP10/00656to L.S.), the Italian Association for Cancer Research (IG 14640to E.L.), the RAS (Sardinian Regional Government to E.L.) andgrants from the National Institute of Environmental HealthSciences (T32ES007015 to C.C. and P30 ES000210 to W.H.B.).P.H. acknowledges the Charles University in Prague projects(UNCE 204015 and PRVOUK P31/2012), by the Czech ScienceFoundation project (P301/12/1686) and by the Internal GrantAgency of the Ministry of Health of the Czech Republic project(NT13663-3/2012). P.K.K. thanks the Center for Environment andWater, Research Institute, KFUPM for research facilities and KingAbdulaziz City for Science and Technology for funding no. T.K.11-0629. V.M.-S. and M.C. thank Canceropôle Rhone-Auvergne (CLARA), La Ligue Nationale Contre le Cancer (Ain, Rhône) andINCA, ANR (ANR-10-LABX-0061 and 2011 ANR-CESA-018-04) andRegion Rhône-Alpes (CMIRA-COOPERA-12-004945-01) grants.D.W.F. acknowledges support from the National Cancer Institute(R01CA17037801, R01CA89305, R01CA105102, P50CA114747,P01CA034233, U56CA112973) and the Leukemia and LymphomaSociety (R6223-07). S.C.C. is currently supported by NationalCancer Institute (F32CA177139), and D.C.K. is supported byNational Cancer Institute (T32CA09151) and a PostdoctoralEnrichment Award from the Burroughs Wellcome fund.
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  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2015-07-15T18:43:38Z No. of bitstreams: 1 BissonWilliamHEnvironmentalMolecularToxicologyEffectEnvironmentalChemicals.pdf: 5045772 bytes, checksum: a31cd46b5b660978c525ed5f45ce006b (MD5)
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2015-07-15T18:44:08Z (GMT) No. of bitstreams: 1 BissonWilliamHEnvironmentalMolecularToxicologyEffectEnvironmentalChemicals.pdf: 5045772 bytes, checksum: a31cd46b5b660978c525ed5f45ce006b (MD5)
  • description.provenance : Made available in DSpace on 2015-07-15T18:44:08Z (GMT). No. of bitstreams: 1 BissonWilliamHEnvironmentalMolecularToxicologyEffectEnvironmentalChemicals.pdf: 5045772 bytes, checksum: a31cd46b5b660978c525ed5f45ce006b (MD5) Previous issue date: 2015-06

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