Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment
Abstract Background Macrophage infiltration in the tumor microenvironment participates in the regulation of tumor progression. Previous studies have found that Notch signaling pathway is involved in regulating the progression of colorectal cancer (CRC), however, the specific mechanism is still uncle...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10526-w |
| _version_ | 1797945900859916288 |
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| author | Kai Huang Wenwu Luo Jinmei Fang Changjun Yu Guangjie Liu Xiaodong Yuan Yun Liu Wenyong Wu |
| author_facet | Kai Huang Wenwu Luo Jinmei Fang Changjun Yu Guangjie Liu Xiaodong Yuan Yun Liu Wenyong Wu |
| author_sort | Kai Huang |
| collection | DOAJ |
| description | Abstract Background Macrophage infiltration in the tumor microenvironment participates in the regulation of tumor progression. Previous studies have found that Notch signaling pathway is involved in regulating the progression of colorectal cancer (CRC), however, the specific mechanism is still unclear. Methods The correlation between Notch signaling pathway and macrophage infiltration was investigated in TCGA database and verified in clinical samples of patients with CRC using immunohistochemistry. Gene Set Enrichment Analysis was used to find out genes related to Notch3 expression. Colony formation assay, and flow cytometry were utilized to test tumor growth and immune cell infiltration in vitro and in vivo. Results Using bioinformatics analysis and clinical sample validation, we found that Notch3 was highly expressed in colon tumor tissues compared to adjacent normal tissues, and it participated in regulating the recruitment of macrophages to the tumor microenvironment. Furthermore, we found that the Notch3 expression was positively correlated with the expression of macrophage recruitment-related cytokines in colon tumor tissues. Finally, we demonstrated that depletion of Notch3 had no significant effect on the growth of colon tumor cells in vitro, while, attenuated the growth of colon cancer tumors in vivo. Simultaneous, immunosuppressive cells, macrophages and myeloid-derived suppressor cell (MDSC) infiltration were dramatically reduced in the tumor microenvironment. Conclusion Our study illustrated that Notch3 could facilitate the progression of CRC by increasing the infiltration of macrophages and MDSCs to promote the immunosuppressive tumor microenvironment. Targeting Notch3 specifically is a potentially effective treatment for CRC. |
| first_indexed | 2024-04-10T21:02:27Z |
| format | Article |
| id | doaj.art-baa1cfb476b6457e962793a19f32eba4 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-10T21:02:27Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-baa1cfb476b6457e962793a19f32eba42023-01-22T12:16:40ZengBMCBMC Cancer1471-24072023-01-0123111110.1186/s12885-023-10526-wNotch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironmentKai Huang0Wenwu Luo1Jinmei Fang2Changjun Yu3Guangjie Liu4Xiaodong Yuan5Yun Liu6Wenyong Wu7Department of Gastrointestinal Surgery, Department of General Surgery, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Pathology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Radiation Oncology, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Gastrointestinal Surgery, Department of General Surgery, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Gastrointestinal Surgery, Department of General Surgery, the First Affiliated Hospital of Anhui Medical UniversityOrgan Transplant Center, Department of Hepatobiliary and Transplantation Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Radiation Oncology, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDepartment of Gastrointestinal Surgery, Department of General Surgery, the First Affiliated Hospital of Anhui Medical UniversityAbstract Background Macrophage infiltration in the tumor microenvironment participates in the regulation of tumor progression. Previous studies have found that Notch signaling pathway is involved in regulating the progression of colorectal cancer (CRC), however, the specific mechanism is still unclear. Methods The correlation between Notch signaling pathway and macrophage infiltration was investigated in TCGA database and verified in clinical samples of patients with CRC using immunohistochemistry. Gene Set Enrichment Analysis was used to find out genes related to Notch3 expression. Colony formation assay, and flow cytometry were utilized to test tumor growth and immune cell infiltration in vitro and in vivo. Results Using bioinformatics analysis and clinical sample validation, we found that Notch3 was highly expressed in colon tumor tissues compared to adjacent normal tissues, and it participated in regulating the recruitment of macrophages to the tumor microenvironment. Furthermore, we found that the Notch3 expression was positively correlated with the expression of macrophage recruitment-related cytokines in colon tumor tissues. Finally, we demonstrated that depletion of Notch3 had no significant effect on the growth of colon tumor cells in vitro, while, attenuated the growth of colon cancer tumors in vivo. Simultaneous, immunosuppressive cells, macrophages and myeloid-derived suppressor cell (MDSC) infiltration were dramatically reduced in the tumor microenvironment. Conclusion Our study illustrated that Notch3 could facilitate the progression of CRC by increasing the infiltration of macrophages and MDSCs to promote the immunosuppressive tumor microenvironment. Targeting Notch3 specifically is a potentially effective treatment for CRC.https://doi.org/10.1186/s12885-023-10526-wNotch3Colorectal tumorTumor microenvironmentMacrophage infiltration |
| spellingShingle | Kai Huang Wenwu Luo Jinmei Fang Changjun Yu Guangjie Liu Xiaodong Yuan Yun Liu Wenyong Wu Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment BMC Cancer Notch3 Colorectal tumor Tumor microenvironment Macrophage infiltration |
| title | Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment |
| title_full | Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment |
| title_fullStr | Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment |
| title_full_unstemmed | Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment |
| title_short | Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment |
| title_sort | notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment |
| topic | Notch3 Colorectal tumor Tumor microenvironment Macrophage infiltration |
| url | https://doi.org/10.1186/s12885-023-10526-w |
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