Activation Of GSK3?/?-CATENIN Pathway Promotes Organ-specific Metastasis In Prostate Cancer

Metastasis is the major cause of treatment failure in various malignancies,including prostate cancer(PCa).Accumulating data has suggested that primary cancer cells prefer to spread to certain organs.To explore the mechanisms of different cancer cells preferentially metastasizing to certain organs,we established a prostate cancer lung metastasis model using luciferase-labeled murine prostate cancer cells(RM1).RM1 cells were injected into the tibia of male C57BL/6J mice(6-7 weeks old)and tumor cell growth and metastasis were monitored every week by Bioluminescence Imaging.The mice were sacrificed when metastatic tumor appeared in multi-organs.We then isolated the lung metastatic tumor,made single cell suspension and amplified.The lung metastatic tumor cells were specifically metastasized to lung when the tumor cells were injected intratibially again.After several cycles we obtained highly lung metastatic tumor cells,named RM1-LM cells.Further,we investigated the property and function changes in RM1-LM cells compared to parental cells(RM1)using in vitro assays.We firstly found the highly lung metastatic tumor cells showed more mesenchymal properties.Western blot results showed that hallmarks of EMT(epithelial-mesenchymal transformation)includingE-cadherin,vimentin,snail,slug and ZEB1 were altered significantly in RM1-LM cells.Then,we observed that the highly lung metastatic tumor cells exhibited increased proliferative,colony formation and migratory abilities.Mechanistic analyses indicated that prostate cancer organ-specific metastasis was mediated by the activation of GSK-3?/?-catenin pathway.The current study not only can lay the foundation for further in-depth research,but also may provide potential therapeutic targets and diagnostic biomarkers of PCa metastasis.