Polychlorinated biphenyls (PCBs) enhance metastatic properties of breast cancer cells by activating Rho-associated kinase (ROCK).
BACKGROUND
Polychlorinated 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, neurotoxicity, estrogenic or antiestrogenic activity, and carcinogenesis. 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.


RESULTS
In 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
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.
Liu
Sijin
S
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China. sjliu@rcees.ac.cn
Li
Shitao
S
Du
Yuguo
Y
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000378:metabolism*
D011078:Polychlorinated Biphenyls; D054460:rho-Associated Kinases