Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity
Abstract Background Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. In this study, we investigated the effects of IL-35 on PCA and its immunoregulatory effect on PCA. Methods The prot...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01583-3 |
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| author | Jialin Zhu Yan Wang Dai Li Haonan Zhang Zhi Guo Xueling Yang |
| author_facet | Jialin Zhu Yan Wang Dai Li Haonan Zhang Zhi Guo Xueling Yang |
| author_sort | Jialin Zhu |
| collection | DOAJ |
| description | Abstract Background Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. In this study, we investigated the effects of IL-35 on PCA and its immunoregulatory effect on PCA. Methods The protein and mRNA expression of IL-35 in PCA cells was detected by western blot and RT-PCR. The invasion and migration of cells were detected using transwell and wound‐healing assays. A CCK-8 assay was conducted to observe cell proliferation. In vivo, IL-35 plasma concentration was test by enzyme-linked immunosorbent assay. The role of IL-35 in tumour cell proliferation and angiogenesis of mice was detected by immunohistochemical stains. The mouse survival and tumour volumes were calculated, and lung metastasis rate was detected by HE staining. The modulatory effects of IL-35 on myeloid-derived inhibitory cells (MDSCs), regulatory T cells (Tregs), CD4+ T cells and CD8+ T cells from PCA mice were investigated by immunohistochemical stains and flow cytometry. Results High levels of IL-35 significantly promoted the migration, invasion and cell proliferation of PCA cells in vitro. IL-35 was associated with tumour growth, metastasis and poor prognosis in PCA mice. Additionally, high levels of IL-35 significantly increased the proportions of MDSCs and Tregs and decreased the proportions of CD4+ and CD8+ T cells in the spleen, blood and tumour microenvironment. The IL-35 neutralizing antibody played the opposite role. Conclusions IL-35 contributed to the progression of PCA through promoting cell proliferation and tumour angiogenesis. IL-35 might limit the anti-tumour immune response by upregulating the proportions of Tregs and MDSCs and by reducing the proportions of CD4+ and CD8+ T cells. IL-35 might serve as a novel therapeutic target for PCA. |
| first_indexed | 2024-12-11T02:56:56Z |
| format | Article |
| id | doaj.art-827f387e25994e1b8eac2039800af0ba |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-11T02:56:56Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-827f387e25994e1b8eac2039800af0ba2022-12-22T01:23:07ZengBMCCancer Cell International1475-28672020-10-0120111310.1186/s12935-020-01583-3Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunityJialin Zhu0Yan Wang1Dai Li2Haonan Zhang3Zhi Guo4Xueling Yang5Department of Ultrasound Diagnosis and Treatment, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Radiology, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Geriatrics, Laboratory of Neuro-Trauma and Neurodegenerative Disorders, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalDepartment of Interventional Therapy, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Interventional Therapy, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalDepartment of Interventional Therapy, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and HospitalAbstract Background Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. In this study, we investigated the effects of IL-35 on PCA and its immunoregulatory effect on PCA. Methods The protein and mRNA expression of IL-35 in PCA cells was detected by western blot and RT-PCR. The invasion and migration of cells were detected using transwell and wound‐healing assays. A CCK-8 assay was conducted to observe cell proliferation. In vivo, IL-35 plasma concentration was test by enzyme-linked immunosorbent assay. The role of IL-35 in tumour cell proliferation and angiogenesis of mice was detected by immunohistochemical stains. The mouse survival and tumour volumes were calculated, and lung metastasis rate was detected by HE staining. The modulatory effects of IL-35 on myeloid-derived inhibitory cells (MDSCs), regulatory T cells (Tregs), CD4+ T cells and CD8+ T cells from PCA mice were investigated by immunohistochemical stains and flow cytometry. Results High levels of IL-35 significantly promoted the migration, invasion and cell proliferation of PCA cells in vitro. IL-35 was associated with tumour growth, metastasis and poor prognosis in PCA mice. Additionally, high levels of IL-35 significantly increased the proportions of MDSCs and Tregs and decreased the proportions of CD4+ and CD8+ T cells in the spleen, blood and tumour microenvironment. The IL-35 neutralizing antibody played the opposite role. Conclusions IL-35 contributed to the progression of PCA through promoting cell proliferation and tumour angiogenesis. IL-35 might limit the anti-tumour immune response by upregulating the proportions of Tregs and MDSCs and by reducing the proportions of CD4+ and CD8+ T cells. IL-35 might serve as a novel therapeutic target for PCA.http://link.springer.com/article/10.1186/s12935-020-01583-3Interleukin-35Prostate cancerProliferationAngiogenesisAnti-tumour immunity |
| spellingShingle | Jialin Zhu Yan Wang Dai Li Haonan Zhang Zhi Guo Xueling Yang Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity Cancer Cell International Interleukin-35 Prostate cancer Proliferation Angiogenesis Anti-tumour immunity |
| title | Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity |
| title_full | Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity |
| title_fullStr | Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity |
| title_full_unstemmed | Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity |
| title_short | Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity |
| title_sort | interleukin 35 promotes progression of prostate cancer and inhibits anti tumour immunity |
| topic | Interleukin-35 Prostate cancer Proliferation Angiogenesis Anti-tumour immunity |
| url | http://link.springer.com/article/10.1186/s12935-020-01583-3 |
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