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  3. Environmental microcystin exposure triggers the poor prognosis of prostate cancer: Evidence from case-control, animal, and in vitro studies

Environmental microcystin exposure triggers the poor prognosis of prostate cancer: Evidence from case-control, animal, and in vitro studies

  • J Environ Sci (China). 2023 May:127:69-81. doi: 10.1016/j.jes.2022.05.051.
Chun Pan 1,  Haixiang Qin 2,  Minghao Yan 1,  Xuefeng Qiu 2,  Wenyue Gong 1,  Wenxin Luo 1,  Hongqian Guo 3,  Xiaodong Han 4
Affiliations

Affiliations

  • 1 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China.
  • 2 Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, China.
  • 3 Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, China. Electronic address: [email protected].
  • 4 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, China. Electronic address: [email protected].
PMID: 36522098 DOI: 10.1016/j.jes.2022.05.051
Abstract

Microcystin-leucine-arginine (MC-LR) is positively linked with multiple cancers in humans. However, the association between MC-LR and the risk and prognosis of prostate Cancer has not been conducted in epidemiological studies. No reported studies have linked MC-LR exposure to the poor prognosis of prostate Cancer by conducting experimental studies. The content of MC-LR was detected in most of the aquatic food in wet markets and supermarkets in Nanjing and posed a health risk for consumers. MC-LR levels in both prostate Cancer tissues and serum were significantly higher than controls. The adjusted odds ratio (OR) for prostate Cancer risk by serum MC-LR was 1.75 (95%CI: 1.21-2.52) in the whole subjects, and a positive correlation between MC-LR and advanced tumor stage was observed. Survival curve analysis indicated patients with higher MC-LR levels in tissues exhibited poorer overall survival. Human, animal, and cell studies confirmed that MC-LR exposure increases the expression of estrogen receptor-α (ERα) and promotes epithelial-mesenchymal transition (EMT) in prostate Cancer. Moreover, MC-LR-induced decreased E-cadherin levels, increased vimentin levels, and increased migratory and invasive capacities of prostate Cancer cells were markedly suppressed upon ERα knockdown. MC-LR-induced xenograft tumor growth and lung metastasis in BALB/c nude mice can be effectively alleviated with ERα knockdown. Our data demonstrated that MC-LR upregulated vimentin and downregulated E-cadherin through activating ERα, promoting migration and invasion of prostate Cancer cells. Our findings highlight the role of MC-LR in prostate Cancer, providing new perspectives to understand MC-LR-induced prostatic toxicity.

Keywords

E-cadherin; Epithelial-mesenchymal transition (EMT); Estrogen receptor-α (ERα); Microcystin-leucine-arginine (MC-LR); Prostate cancer; Vimentin.

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