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• W2922279286 abstract "Abstract Known as co-stimulatory molecule, programmed death ligand-2 (PD-L2) contributes to T-cell exhaustion by interaction with programmed death-1 (PD-1) receptor, but its tumor cell-intrinsic signal effects have been little investigated. PD-L2 expression was detected by immunohistochemistry in 18 pairs of primary osteosarcoma tissues and matching lung metastasis tissues. We also investigated the effects of PD-L2 knockdown on osteosarcoma both in vitro and in vivo. In our study, PD-L2 expression was elevated in lung metastases compared with primary osteosarcoma according to an immunohistochemistry assay. Wound-healing and transwell assays revealed that PD-L2 knockdown leaded to inhibition of migration and invasion of human osteosarcoma cells in vitro. Mechanistically, we demonstrated that PD-L2 knockdown attenuated migration and invasion by inactivating RhoA-ROCK-LIMK2 signaling, suppressing epithelial–mesenchymal transition (EMT), and inhibiting autophagy by decreasing beclin-1 expression. In support of these observations, beclin-1 knockdown also inhibited activation of the RhoA-ROCK-LIMK2 pathway, leading to autophagy inhibition-induced blockade of migration and invasion. Depletion of PD-L2 in KHOS cells markedly weakens pulmonary metastatic potential in vivo by orthotopic transplantation of nude mice. Our study reveals a pro-metastatic functional mechanism for PD-L2 in osteosarcoma. Furthermore, we demonstrate a regulatory role for PD-L2 on autophagy, as well as a relationship between autophagy and metastasis in osteosarcoma, which may represent a potential therapeutic target for osteosarcoma." @default.
• W2922279286 created "2019-03-22" @default.
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• W2922279286 date "2019-03-18" @default.
• W2922279286 modified "2023-10-18" @default.
• W2922279286 title "Osteosarcoma cell intrinsic PD-L2 signals promote invasion and metastasis via the RhoA-ROCK-LIMK2 and autophagy pathways" @default.
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• W2922279286 doi "https://doi.org/10.1038/s41419-019-1497-1" @default.
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• W2922279286 hasPublicationYear "2019" @default.
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