Abstract | BACKGROUND: Recent studies indicated that exosomal programmed death-ligand 1 (PD-L1) derived from cancers could induce immunosuppression and tumor pathogenesis. However, it is unclear how exosomes influence osteosarcoma (OS) progression and whether PD-L1 also exists in serum exosomes (Sr-exosomes) of patients with osteosarcoma. We examined serum exosomes from 70 OS patients, 9 patients with benign tumors and 22 healthy donors. OS-derived exosomes were functionally evaluated in vivo and in vitro. RESULTS: The characteristics of exosomes derived from OS patient serum and OS cell lines were confirmed by several methods. We found OS patients had a higher level of exosomal PD-L1 compared to healthy donors. Meanwhile, OS patients with pulmonary metastasis also showed a relatively higher level of exosomal PD-L1 than patients without metastasis. Next, bioinformatic analysis demonstrated that Sr-exosomes isolated from OS patients may involve in the important process of immune function and cancer pathogenesis for OS patients. Co-expression network centered with PD-L1 among Sr-exosomal differently expressed mRNA demonstrated exosomal N-cadherin had a close relationship with exosomal PD-L1 expression. Then, we confirmed higher level of Sr-exosomal N-cadherin in OS patients with pulmonary metastasis compared to ones without metastasis. Furthermore, we elucidated osteosarcoma-derived exosomes and exosomal-PD-L1 promoted the pulmonary metastasis in metastatic models. ROC (Receiver Operating Characteristic Curve) analysis showed AUC (Area Under Curve) of 0.823 for exosomal PD-L1, 0.806 for exosomal N-cadherin and 0.817 for exosomal N-cadherin/ E-cadherin to distinguish OS patients with pulmonary metastasis from ones without metastasis. CONCLUSIONS:
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Authors | Jun Wang, Hongliang Zhang, Xin Sun, Xiaofang Wang, Tingting Ren, Yi Huang, Ranxin Zhang, Bingxin Zheng, Wei Guo |
Journal | Journal of nanobiotechnology
(J Nanobiotechnology)
Vol. 18
Issue 1
Pg. 151
(Oct 22 2020)
ISSN: 1477-3155 [Electronic] England |
PMID | 33092576
(Publication Type: Journal Article)
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Chemical References |
- B7-H1 Antigen
- Biomarkers, Tumor
- CD274 protein, human
- Cadherins
- RNA, Messenger
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Topics |
- Animals
- B7-H1 Antigen
(blood, genetics)
- Biomarkers, Tumor
(blood)
- Cadherins
(blood, genetics)
- Cell Line, Tumor
- Cell Membrane Permeability
- Computational Biology
- Disease Progression
- Exosomes
(chemistry)
- Female
- Gene Knockdown Techniques
- Humans
- Lung Neoplasms
(diagnosis, secondary)
- Mice, Inbred BALB C
- Neoplasm Metastasis
(diagnosis)
- Osteosarcoma
(metabolism)
- RNA, Messenger
(metabolism)
- Tissue Distribution
- Wound Healing
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