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Poster Display session

301 - Osteosarcoma cell intrinsic PD-L2 signals promote invasion and metastasis via the RhoA-ROCK-LIMK2 and autophagy pathways


14 Dec 2018


Poster Display session




Annals of Oncology (2018) 29 (suppl_10): x1-x10. 10.1093/annonc/mdy493


T. Ren, B. Zheng, W. Guo

Author affiliations

  • Musculoskeletal Tumor Center, Peking University People's Hospital, 100044 - Beijing/CN


Abstract 301


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 has 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 leads 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 beclin1 expression. In support of these observations, beclin1 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.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Tingting Ren.


Has not received any funding.


All authors have declared no conflicts of interest.

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