The impact of cadmium exposure on renal cell carcinoma progression and metastasis
As of 2025, kidney cancer is the seventh most common cancer according to the National Institutes of Health. Renal cell carcinoma (RCC), the predominant form of kidney cancer, has been linked to environmental exposures, including toxic metals. Cadmium (Cd), a widespread environmental contaminant associated with multiple adverse health effects, enters the body primarily through smoking, diet, or occupational exposure. Elevated blood Cd levels have been observed in RCC patients, and meta-analyses of observational studies have established a positive association between Cd exposure and increased RCC risk. Evidence from previous studies further suggests that Cd may modulate proteins involved in the epithelial-to-mesenchymal transition (EMT), a key process in cancer progression and metastasis. To explore the role of Cd in RCC progression, we examined the effects of subchronic Cd exposure on Renca cells, a murine RCC cell line. Cells were treated with 0.5 µM Cd for one passage (acute exposure) or 10–21 passages (subchronic exposure). We assessed cell proliferation, colony formation, and protein/gene expression via Western blotting and qPCR. Subchronic Cd exposure significantly enhanced proliferation and colony formation in Renca cells compared to controls. It also upregulated estrogen receptor alpha (ER[alpha]) gene expression, consistent with Cd's known metalloestrogenic activity. Conditioned medium from Cd challenged cells stimulated proliferation in untreated control cells, indicating activation of an autocrine growth-promoting pathway. Additionally, acute exposure to Cd reduced E-cadherin expression, a hallmark of EMT induction. These findings demonstrate that subchronic Cd exposure promotes RCC cell proliferation in vitro. Potential underlying mechanisms include elevated ER[alpha] and TGF-[beta] signaling, which may contribute to enhanced metastatic potential via EMT. These results highlight Cd as a relevant environmental modifier of RCC progression and underscore the need for further investigation into its clinical implications for metastasis and disease management via in vivo mouse models currently in development.