A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer
Abstract Background Research has indicated that the emergence of Schwann cells around premalignant lesions of colon cancer might be an early indicator promoting the onset of tumorigenesis. The present study explored the communication between colon cancer cells and Schwann cells. Methods Immunofluore...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-022-02556-2 |
| _version_ | 1811291416068882432 |
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| author | Shengbo Han Decai Wang Yan Huang Zhu Zeng Peng Xu Hewei Xiong Zunxiang Ke Ya Zhang Yuhang Hu Fan Wang Jie Wang Yong Zhao Wenfeng Zhuo Gang Zhao |
| author_facet | Shengbo Han Decai Wang Yan Huang Zhu Zeng Peng Xu Hewei Xiong Zunxiang Ke Ya Zhang Yuhang Hu Fan Wang Jie Wang Yong Zhao Wenfeng Zhuo Gang Zhao |
| author_sort | Shengbo Han |
| collection | DOAJ |
| description | Abstract Background Research has indicated that the emergence of Schwann cells around premalignant lesions of colon cancer might be an early indicator promoting the onset of tumorigenesis. The present study explored the communication between colon cancer cells and Schwann cells. Methods Immunofluorescence analyses were conducted to examine the differential distribution of Schwann cells within colon cancer tissues and normal colon tissues. CCK8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the interaction between colon cancer cells and Schwann cells. Exosomes derived from colon cancer cells were isolated to further explore the effect of colon cancer cells on Schwann cells. Gain- and loss-of function experiments, luciferase reporter assays, chromatin immunoprecipitation assays, and immunohistochemistry assays were performed to reveal the cross-talk between colon cancer cells and Schwann cells. Furthermore, colon cancer cells co-cultured with Schwann cells were transplanted into nude mice for evaluating their effect on tumor proliferation and metastasis in vivo. Results The clinicopathological characteristics indicated that Schwann cells were enriched in colon cancer tissues and were associated with tumor metastasis and poor prognosis. The co-culture of Schwann cells with colon cancer cells promoted the proliferation and migration of colon cancer cells and Schwann cells, which was mediated by nerve growth factor (NGF) secreted from Schwann cells. Exosomal miR-21-5p released by colon cancer cells inhibited VHL expression in Schwann cells, which in turn stabilized the HIF-1α protein and increased the transcription of NGF. Meanwhile, the Schwann cells-derived NGF activated TrkA/ERK/ELK1/ZEB1 signaling pathway in colon cancer cells, which further enhanced the expression of exosomal miR-21-5p. Inhibition of either NGF or miR-21-5p significantly inhibited the proliferation and metastasis of transplanted colon cancer cells in nude mice. Coincidently, miR-21-5p was positively associated with the expression of NGF, p-ERK, p-ELK1, and ZEB1 in human colon cancer tissues. Conclusions Our results implicated a reciprocal communication between colon cancer cells and Schwan cells that promoted the proliferation and metastasis of colon cancer, and identified NGF and exosomal miR-21-5p as potential therapeutic targets for the treatment of colon cancer. |
| first_indexed | 2024-04-13T04:29:03Z |
| format | Article |
| id | doaj.art-e457258ad1bc49aeb7537503db9cc123 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T04:29:03Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-e457258ad1bc49aeb7537503db9cc1232022-12-22T03:02:24ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662022-12-0141112310.1186/s13046-022-02556-2A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancerShengbo Han0Decai Wang1Yan Huang2Zhu Zeng3Peng Xu4Hewei Xiong5Zunxiang Ke6Ya Zhang7Yuhang Hu8Fan Wang9Jie Wang10Yong Zhao11Wenfeng Zhuo12Gang Zhao13Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Research has indicated that the emergence of Schwann cells around premalignant lesions of colon cancer might be an early indicator promoting the onset of tumorigenesis. The present study explored the communication between colon cancer cells and Schwann cells. Methods Immunofluorescence analyses were conducted to examine the differential distribution of Schwann cells within colon cancer tissues and normal colon tissues. CCK8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the interaction between colon cancer cells and Schwann cells. Exosomes derived from colon cancer cells were isolated to further explore the effect of colon cancer cells on Schwann cells. Gain- and loss-of function experiments, luciferase reporter assays, chromatin immunoprecipitation assays, and immunohistochemistry assays were performed to reveal the cross-talk between colon cancer cells and Schwann cells. Furthermore, colon cancer cells co-cultured with Schwann cells were transplanted into nude mice for evaluating their effect on tumor proliferation and metastasis in vivo. Results The clinicopathological characteristics indicated that Schwann cells were enriched in colon cancer tissues and were associated with tumor metastasis and poor prognosis. The co-culture of Schwann cells with colon cancer cells promoted the proliferation and migration of colon cancer cells and Schwann cells, which was mediated by nerve growth factor (NGF) secreted from Schwann cells. Exosomal miR-21-5p released by colon cancer cells inhibited VHL expression in Schwann cells, which in turn stabilized the HIF-1α protein and increased the transcription of NGF. Meanwhile, the Schwann cells-derived NGF activated TrkA/ERK/ELK1/ZEB1 signaling pathway in colon cancer cells, which further enhanced the expression of exosomal miR-21-5p. Inhibition of either NGF or miR-21-5p significantly inhibited the proliferation and metastasis of transplanted colon cancer cells in nude mice. Coincidently, miR-21-5p was positively associated with the expression of NGF, p-ERK, p-ELK1, and ZEB1 in human colon cancer tissues. Conclusions Our results implicated a reciprocal communication between colon cancer cells and Schwan cells that promoted the proliferation and metastasis of colon cancer, and identified NGF and exosomal miR-21-5p as potential therapeutic targets for the treatment of colon cancer.https://doi.org/10.1186/s13046-022-02556-2Schwann cellsColon cancerMetastasisExosomesNGFEMT |
| spellingShingle | Shengbo Han Decai Wang Yan Huang Zhu Zeng Peng Xu Hewei Xiong Zunxiang Ke Ya Zhang Yuhang Hu Fan Wang Jie Wang Yong Zhao Wenfeng Zhuo Gang Zhao A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer Journal of Experimental & Clinical Cancer Research Schwann cells Colon cancer Metastasis Exosomes NGF EMT |
| title | A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer |
| title_full | A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer |
| title_fullStr | A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer |
| title_full_unstemmed | A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer |
| title_short | A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer |
| title_sort | reciprocal feedback between colon cancer cells and schwann cells promotes the proliferation and metastasis of colon cancer |
| topic | Schwann cells Colon cancer Metastasis Exosomes NGF EMT |
| url | https://doi.org/10.1186/s13046-022-02556-2 |
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