Autocrine osteopontin is involved in maintaining the growth and metastasis of Echinococcus multilocularis
Hai-Cheng Yang1, Hong-Wei Zhang2, Jian Yang2
1The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang, China; School of Medicine, Shihezi University, Shihezi, Xinjiang, China.
Abstract:
Alveolar echinococcosis is a zoonotic disease that seriously endangers human health. This study aims to investigate the effects of osteopontin on the growth and intra- or extra-hepatic metastasis of Echinococcus multilocularis. Mice were randomly divided into untreated (control group, n = 25), PBS (n = 25), Lv3-NC (n = 25), and Lv-OPN-734 (n = 25) groups. Knockdown OPN by injecting lentivirus through the intraperitoneal portal vein, the metastatic lesions infected with Echinococcus multilocularis and adjacent liver tissues were observed, and the expression of osteopontin and epidermal growth factor receptor pathway-related molecules were studied. Gross observation of specimens suggested that there was no extra- hepatic metastasis, and mild intrahepatic invasion was observed in the Lv-OPN-734 group after 4 months of infection, and lung metastasis occurred in the Lv3-NC group. Western-blot and immunohistochemical staining results showed that the protein expression of OPN, phosphorylation of epidermal growth factor receptor and downstream molecules of the pathway decreased significantly after osteopontin knockdown, whereas the levels of non-phosphorylated proteins did not change significantly. In human tissues, through western-blot and immunohistochemical staining we found that compared with the control group, the expression of OPN in the liver tissues infected with Echinococcus multilocularis were higher than that in the control group. These findings indicate that osteopontin is involved in maintaining the growth and metastasis of Echinococcus multilocularis, suggesting that osteopontin may be a potential target for the treatment of alveolar echinococcosis.
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