Potential Pro-Tumorigenic Effect of Bisphenol A in Breast Cancer via Altering the Tumor Microenvironment

Abstract

BPA, a chemical used in the preparation of polycarbonate plastics, is an endocrine disruptor. Exposure to BPA has been suggested to be a risk factor for breast cancer because of its potential to induce estrogen receptor signaling in breast cancer cells. More recently, it has been recognized that BPA also binds to the G protein-coupled estrogen receptor and other nuclear receptors, in addition to estrogen receptors, and acts on immune cells, adipocytes, and fibroblasts, potentially modulating the TME. The TME significantly impacts the behavior of cancer cells. Therefore, understanding how BPA affects stromal components in breast cancer is imperative to adequately assess the association between exposure to BPA and the risk of breast cancer. This review examines the effects of BPA on stromal components of tumors to highlight their potential role in the carcinogenic effect of BPA. As a result, I propose considerations for the risk assessment of BPA exposure and studies needed to improve understanding of the TME-mediated, breast cancer-promoting effect of BPA.

Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response

“…Female Mongolian gerbils ( Meriones unguiculatus ) were allocated with fertile males in reproductive age (4 months old) for allowing copulation. On the 8th gestational day, the pregnant females were sorted into four experimental groups ( n = 8): control (subjected to water gavage/daily); vehicle (subjected to 0.1 ml corn oil gavage/daily); ↓BPA (subjected to 50 µg/kg of BPA/daily in corn oil by gavage/daily—reference dose with carcinogenic effects; see Ruiz, Colleta, Leonel, et al (2021); Ruiz, Colleta, Zuccari et al (2021) and Kwon (2022); BPA, Merck Milllipore, 239658); and ↑BPA (subjected to 5000 µg/kg of BPA/daily—high dose). Gavage was performed for 39 days—18 days of pregnancy and 21 days of lactation.…”

Bisphenol-A in Drinking Water Accelerates Mammary Cancerogenesis and Favors an Immunosuppressive Tumor Microenvironment in BALB–neuT Mice

“…Moreover, BPA exposure can lead to the activation of other signaling pathways, such as Akt/PI3K or JAK-STAT pathways, and to the abnormal regulation of p53 expression in breast cancer [ 5 , 45 ]. Furthermore, besides its effects on cancer cells, BPA has been reported to affect the properties of the tumor microenvironment and to alter immune surveillance, thereby potentially exerting additional detrimental effects on breast cancer progression [ 46 , 47 , 48 ].…”

Simple high‐performance liquid chromatography‐ultraviolet method for simultaneous separation and detection of 14 bisphenol pollutants in building materials

“…However, the harmful effects of these pollutants on human health and the ecosystem have been increasingly reported. For instance, BPA has been recognized as a typical endocrine-disrupting chemical that is highly associated with numerous diseases such as breast [7,8] and prostatic cancers [9,10]. BPS, BPF, and BPAF are known for their carcinogenicity, reproductive toxicity, genotoxicity, and endocrine disruption potential, as they can induce oxidative stress and DNA damage, decrease enzyme activity, and interfere with the thyroid hormone signaling pathway [11][12][13][14].…”