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The effect of environmental chemicals on the tumor microenvironment
Stephanie C Casey1, Monica Vaccari2, Fahd Al-Mulla3
1Division of Oncology, Departments of Medicine and Pathology, Stanford University, Stanford, CA 94305, USA, Center for Environmental Carcinogenesis and Risk Assessment, Environmental Protection and Health Prevention Agency, 40126 Bologna, Italy, Department of Pathology, Kuwait University, 13110 Safat, Kuwait, Department of Experimental and Clinical Medicine, University of Firenze, 50134 Florence, Italy, Department of Radiation Oncology, NYU School of Medicine, New York, NY 10016, USA, Department of Environmental and Radiological Health Sciences, Colorado State University/ Colorado School of Public Health, Fort Collins, CO 80523-1680, USA, Centre De Recherche En Cancerologie De Lyon, U1052-UMR5286, Université de Lyon, 69007 Lyon, France, Cancer Research UK, Cambridge Institute, University of Cambridge, Robinson Way, CB2 0RE Cambridge, UK, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA, Mediterranean Institute of Oncology, 95029 Viagrande, Italy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia, Charles University in Prague, Third Faculty of Medicine, 100 00 Prague 10, Czech Republic, Center for Environment and Water, Research Institute, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia, Department of Science and Biomedical Technology, University of Cagliari, 09124 Cagliari, Italy, Pathology Unit, Mediterranean Institute of Oncology, 95029 Viagrande, Italy, Institute of Molecular Genetics, National Research Council, 27100 Pavia, Italy, Regulatory Toxicology Research Division, Bureau of Chemical Safety Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario K1A0K9, Canada, Department of Medicine, University of Louisville, Louisville, KY 40202, USA, Molecular Oncology Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC 20057, USA, University of Pennsylvania School of Medicine
Abstract:
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.
Insights
Environmental exposures, including disruptive chemicals and pharmaceuticals, can alter the tumor microenvironment, influencing cancer development. Understanding these interactions is crucial for cancer etiology and prevention strategies.
Area of Science:
- Oncology
- Toxicology
- Environmental Health
Background:
- Carcinogens can induce cancer via direct DNA damage or indirect cellular effects.
- The tumor microenvironment, comprising vascular networks, extracellular matrix, signaling molecules, and immune cells, plays a critical role in tumor development.
- Environmental exposures can disrupt the tumor microenvironment, affecting cancer progression.
Purpose of the Study:
- To review how environmental exposures perturb the tumor microenvironment.
- To highlight the role of specific chemicals and pharmaceuticals in disrupting the tumor microenvironment.
Main Methods:
- Literature review of carcinogens and their effects on the tumor microenvironment.
- Analysis of how environmental factors influence cellular and molecular components of the tumor microenvironment.
Main Results:
- Potentially carcinogenic compounds, including specific chemicals (nickel chloride, Bisphenol A, butyltins, methylmercury, paraquat) and pharmaceuticals (diabetes medications), can disrupt the tumor microenvironment.
- Carcinogens impact epithelial cells, stromal cells, extracellular matrix, and immune cells within the tumor microenvironment.
Conclusions:
- Environmental exposures significantly influence tumor development by altering the tumor microenvironment.
- Further research into dose-dependent effects of chemical mixtures on the tumor microenvironment is needed for understanding cancer etiology and prevention.
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