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

• Published in: Journal of environmental sciences (China) Vol. 127; pp. 69 - 81
• Main Authors: Pan, Chun, Qin, Haixiang, Yan, Minghao, Qiu, Xuefeng, Gong, Wenyue, Luo, Wenxin, Guo, Hongqian, Han, Xiaodong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2023
• Subjects: Animals; blood serum; Cadherins; Case-Control Studies; China; E-cadherin; Epithelial-mesenchymal transition (EMT); Estrogen Receptor alpha; Estrogen receptor-α (ERα); estrogens; Humans; lungs; Male; metastasis; Mice; Mice, Nude; Microcystin-leucine-arginine (MC-LR); microcystin-LR; Microcystins - toxicity; migratory behavior; odds ratio; prognosis; Prostate cancer; Prostatic Neoplasms; risk; toxicity; Vimentin; xenotransplantation; China; Vimentin; Epithelial-mesenchymal transition (EMT); Prostate cancer; E-cadherin; Microcystin-leucine-arginine (MC-LR); Estrogen receptor-α (ERα)
• ISSN: 1001-0742; 1878-7320
• DOI: 10.1016/j.jes.2022.05.051

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. [Display omitted]