Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients
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-exo...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-020-00710-6 |
| _version_ | 1818001995261280256 |
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| author | Jun Wang Hongliang Zhang Xin Sun Xiaofang Wang Tingting Ren Yi Huang Ranxin Zhang Bingxin Zheng Wei Guo |
| author_facet | Jun Wang Hongliang Zhang Xin Sun Xiaofang Wang Tingting Ren Yi Huang Ranxin Zhang Bingxin Zheng Wei Guo |
| author_sort | Jun Wang |
| collection | DOAJ |
| description | 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 Osteosarcoma stimulates pulmonary metastasis by releasing exosomes, that carry PD-L1 and N-cadherin. Detection of exosomal PD-L1 and N-cadherin from serum of OS patients may predict pulmonary metastasis progression for OS patients. |
| first_indexed | 2024-04-14T03:41:12Z |
| format | Article |
| id | doaj.art-22156c2ee5d84f5f9378fb6cb89f56e2 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T03:41:12Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-22156c2ee5d84f5f9378fb6cb89f56e22022-12-22T02:14:31ZengBMCJournal of Nanobiotechnology1477-31552020-10-0118112310.1186/s12951-020-00710-6Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patientsJun Wang0Hongliang Zhang1Xin Sun2Xiaofang Wang3Tingting Ren4Yi Huang5Ranxin Zhang6Bingxin Zheng7Wei Guo8Peking University People’s Hospital, Musculoskeletal Tumor CenterPeking University People’s Hospital, Musculoskeletal Tumor CenterPeking University People’s Hospital, Musculoskeletal Tumor CenterBeijing Key Laboratory of Bio-Characteristic Profiling for Evaluation of Rational Drug Use, International Cooperation & Joint Laboratoryof Bio-Characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University,Peking University People’s Hospital, Musculoskeletal Tumor CenterPeking University People’s Hospital, Musculoskeletal Tumor CenterPeking University People’s Hospital, Musculoskeletal Tumor CenterPeking University People’s Hospital, Musculoskeletal Tumor CenterPeking University People’s Hospital, Musculoskeletal Tumor CenterAbstract 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 Osteosarcoma stimulates pulmonary metastasis by releasing exosomes, that carry PD-L1 and N-cadherin. Detection of exosomal PD-L1 and N-cadherin from serum of OS patients may predict pulmonary metastasis progression for OS patients.http://link.springer.com/article/10.1186/s12951-020-00710-6Exosomeprogrammed death-ligand 1N-cadherinosteosarcomabiomarker |
| spellingShingle | Jun Wang Hongliang Zhang Xin Sun Xiaofang Wang Tingting Ren Yi Huang Ranxin Zhang Bingxin Zheng Wei Guo Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients Journal of Nanobiotechnology Exosome programmed death-ligand 1 N-cadherin osteosarcoma biomarker |
| title | Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients |
| title_full | Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients |
| title_fullStr | Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients |
| title_full_unstemmed | Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients |
| title_short | Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients |
| title_sort | exosomal pd l1 and n cadherin predict pulmonary metastasis progression for osteosarcoma patients |
| topic | Exosome programmed death-ligand 1 N-cadherin osteosarcoma biomarker |
| url | http://link.springer.com/article/10.1186/s12951-020-00710-6 |
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