Abstract
BackgroundPolychlorinated biphenyls (PCBs) are a family of structurally related chlorinated aromatic hydrocarbons. Numerous studies have documented a wide spectrum of biological effects of PCBs on human health, such as immunotoxicity, neurotoxocity, estrogenic or antiestrogenic activity, and carcinogensis. The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo, animal and epidemiologic studies. A number of investigations indicated that higher levels of PCBs in mammary tissues or sera correlated to breast cancer risk, and PCBs might be implicated in advancing breast cancer progression.Methodology/Principal FindingsIn the current study, we for the first time report that PCBs greatly promote the ROCK activity and therefore increase cell motility for both non-metastatic and metastatic human breast cancer cells in vitro. In the in vivo study, PCBs significantly advance disease progression, leading to enhanced capability of metastatic breast cancer cells to metastasize to bone, lung and liver. Additionally, PCBs robustly induce the production of intracellular reactive oxygen species (ROS) in breast cancer cells; ROS mechanistically elevate ROCK activity.Conclusions/SignificancePCBs enhance the metastatic propensity of breast cancer cells by activating the ROCK signaling, which is dependent on ROS induced by PCBs. Inhibition of ROCK may stand for a unique way to restrain metastases in breast cancer upon PCB exposure.
Highlights
Polychlorinated biphenyls (PCBs) are chlorinated aromatic hydrocarbons with 209 congeners
Conclusions/Significance: PCBs enhance the metastatic propensity of breast cancer cells by activating the Rho-Associated Kinase (ROCK) signaling, which is dependent on reactive oxygen species (ROS) induced by PCBs
We describe a novel role of PCBs in enhancing metastatic properties of breast cancer cells by activating the ROCK signaling
Summary
Polychlorinated biphenyls (PCBs) are chlorinated aromatic hydrocarbons with 209 congeners. Conclusions/Significance: PCBs enhance the metastatic propensity of breast cancer cells by activating the ROCK signaling, which is dependent on ROS induced by PCBs. Inhibition of ROCK may stand for a unique way to restrain metastases in breast cancer upon PCB exposure. Clinical studies show that the expression of ROCK is significantly increased in human breast cancer tumors with metastases than those without metastases [15,16].
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