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Journal of Hazardous Materials

Journal of Hazardous Materials

IF: 12.2
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Bisphenols exposure at environmentally relevant dose promoted ovarian cancer progression and modulated tumor microenvironment through β-catenin/SPP1 axis

Published:3 March 2025 DOI: 10.1016/j.jhazmat.2025.137824
Sinan Xu, Xiaoyu Yuan, Yuwei Wang, Zhiqin Fu, Kelie Chen, Zhenyan Cui, Leting Xu, Honghe Zhang, Dajing Xia, Yihua Wu

Abstract

Bisphenol A (BPA) and its substitute, Bisphenol S (BPS) are typical endocrine-disrupting chemicals used in plastics, but their cancer-promoting effect has remained controversial. Here, we investigated the effects of environmentally relevant doses of BPA/BPS exposure on the tumor microenvironment (TME) in ovarian cancer. BPA exposure levels was exhibiting a declining trend and BPS showing an ascending trend in the female population by analyzing the NHANES data (2013-2016). Low doses of BPA/BPS both significantly promoted the migration and invasion of ovarian cancer cells in a dose-dependent manner by activating the Wnt/β-catenin signaling pathway, thereby facilitating the SPP1 gene transcription. Notably, low-dose BPA/BPS exposure stimulated ovarian cancer cells to secrete OPN protein (coded by the SPP1 gene), subsequently inducing the transformation of fibroblasts into cancer-associated fibroblasts (CAFs), which could reshape the TME of ovarian cancer. Two in-vivo experiments established with nude mice and SPP1-/- mice respectively, both confirmed that low-dose BPA/BPS exposure increased the incidence of tumor metastasis accompanied by CAF infiltration, while administration of OPN-neutralizing antibodies effectively blocked these effects. Our results indicated that exposure to either BPA or its substitute BPS could promote the release of secreted protein OPN via the β-catenin/SPP1 axis, ultimately modulating the TME and enhancing the progression of ovarian cancer, providing new evidence and potential intervention strategies for the toxicological assessment and management of bisphenols.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
ICG-001 847591-62-2 C33H32N4O4 145 suppliers $28.00-$2200.00
ICG-001 847591-62-2 C33H32N4O4 145 suppliers $28.00-$2200.00
ICG-001 847591-62-2 C33H32N4O4 145 suppliers $28.00-$2200.00
ICG-001 847591-62-2 C33H32N4O4 145 suppliers $28.00-$2200.00

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