A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells
Small-cell lung cancer (SCLC), representing 15–20% of all lung cancers, is an aggressive malignancy with a distinct natural history, poor prognosis, and limited treatment options. We have previously identified Schwann cells (SCs), the main glial cells of the peripheral nervous system, in tumor tissu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/24/6132 |
| _version_ | 1797461091581689856 |
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| author | Shuhui Cao Yue Wang Yan Zhou Yao Zhang Xuxinyi Ling Lincheng Zhang Jingwen Li Yu Yang Weimin Wang Michael R. Shurin Hua Zhong |
| author_facet | Shuhui Cao Yue Wang Yan Zhou Yao Zhang Xuxinyi Ling Lincheng Zhang Jingwen Li Yu Yang Weimin Wang Michael R. Shurin Hua Zhong |
| author_sort | Shuhui Cao |
| collection | DOAJ |
| description | Small-cell lung cancer (SCLC), representing 15–20% of all lung cancers, is an aggressive malignancy with a distinct natural history, poor prognosis, and limited treatment options. We have previously identified Schwann cells (SCs), the main glial cells of the peripheral nervous system, in tumor tissues and demonstrated that they may support tumor spreading and metastasis formation in the in vitro and in vivo models. However, the role of SCs in the progression of SCLC has not been investigated. To clarify this issue, the cell proliferation assay, the annexin V apoptosis assay, and the transwell migration and invasion assay were conducted to elucidate the roles in SCLC of tumor-associated SCs (TA-SCs) in the proliferation, apoptosis, migration, and invasion of SCLC cells in vitro, compared to control group. In addition, the animal models to assess SC action’s effects on SCLC in vivo were also developed. The result confirmed that TA-SCs have a well-established and significant role in facilitating SCLC cell cancer migration and invasion of SCLC in vitro, and we also observed that SC promotes tumor growth of SCLC in vivo and that TA-SCs exhibited an advantage and show a repair-like phenotype, which allowed defining them as tumor-associated repair SCs (TAR-SCs). Potential molecular mechanisms of pro-tumorigenic activity of TAR-SCs were investigated by the screening of differentially expressed genes and constructing networks of messenger-, micro-, and long- non-coding RNA (mRNA-miRNA-lncRNA) using DMS114 cells, a human SCLC, stimulated with media from DMS114-activated SCs, non-stimulated SCs, and appropriate controls. This study improves our understanding of how SCs, especially tumor-activated SCs, may promote SCLC progression. Our results highlight a new functional phenotype of SCs in cancer and bring new insights into the characterization of the nervous system-tumor crosstalk. |
| first_indexed | 2024-03-09T17:14:29Z |
| format | Article |
| id | doaj.art-89e18e5d245945bcba00006a329a7bb7 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:14:29Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-89e18e5d245945bcba00006a329a7bb72023-11-24T13:46:43ZengMDPI AGCancers2072-66942022-12-011424613210.3390/cancers14246132A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann CellsShuhui Cao0Yue Wang1Yan Zhou2Yao Zhang3Xuxinyi Ling4Lincheng Zhang5Jingwen Li6Yu Yang7Weimin Wang8Michael R. Shurin9Hua Zhong10Department of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USADepartment of Pulmonary, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaSmall-cell lung cancer (SCLC), representing 15–20% of all lung cancers, is an aggressive malignancy with a distinct natural history, poor prognosis, and limited treatment options. We have previously identified Schwann cells (SCs), the main glial cells of the peripheral nervous system, in tumor tissues and demonstrated that they may support tumor spreading and metastasis formation in the in vitro and in vivo models. However, the role of SCs in the progression of SCLC has not been investigated. To clarify this issue, the cell proliferation assay, the annexin V apoptosis assay, and the transwell migration and invasion assay were conducted to elucidate the roles in SCLC of tumor-associated SCs (TA-SCs) in the proliferation, apoptosis, migration, and invasion of SCLC cells in vitro, compared to control group. In addition, the animal models to assess SC action’s effects on SCLC in vivo were also developed. The result confirmed that TA-SCs have a well-established and significant role in facilitating SCLC cell cancer migration and invasion of SCLC in vitro, and we also observed that SC promotes tumor growth of SCLC in vivo and that TA-SCs exhibited an advantage and show a repair-like phenotype, which allowed defining them as tumor-associated repair SCs (TAR-SCs). Potential molecular mechanisms of pro-tumorigenic activity of TAR-SCs were investigated by the screening of differentially expressed genes and constructing networks of messenger-, micro-, and long- non-coding RNA (mRNA-miRNA-lncRNA) using DMS114 cells, a human SCLC, stimulated with media from DMS114-activated SCs, non-stimulated SCs, and appropriate controls. This study improves our understanding of how SCs, especially tumor-activated SCs, may promote SCLC progression. Our results highlight a new functional phenotype of SCs in cancer and bring new insights into the characterization of the nervous system-tumor crosstalk.https://www.mdpi.com/2072-6694/14/24/6132small-cell lung cancerSchwann cellstumor progressionmiRNAgene expression |
| spellingShingle | Shuhui Cao Yue Wang Yan Zhou Yao Zhang Xuxinyi Ling Lincheng Zhang Jingwen Li Yu Yang Weimin Wang Michael R. Shurin Hua Zhong A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells Cancers small-cell lung cancer Schwann cells tumor progression miRNA gene expression |
| title | A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells |
| title_full | A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells |
| title_fullStr | A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells |
| title_full_unstemmed | A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells |
| title_short | A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells |
| title_sort | novel therapeutic target for small cell lung cancer tumor associated repair like schwann cells |
| topic | small-cell lung cancer Schwann cells tumor progression miRNA gene expression |
| url | https://www.mdpi.com/2072-6694/14/24/6132 |
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