BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway
Abstract Background Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. Bone morphogenetic protein (BMP) exhibits a broad spectrum of biological activities in various tissues including angiogenesis. Here, this study aimed t...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1301-2 |
| _version_ | 1811292263222870016 |
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| author | Peng-Cheng Feng Xing-Fei Ke Hui-Lan Kuang Li-Li Pan Qiang Ye Jian-Bing Wu |
| author_facet | Peng-Cheng Feng Xing-Fei Ke Hui-Lan Kuang Li-Li Pan Qiang Ye Jian-Bing Wu |
| author_sort | Peng-Cheng Feng |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. Bone morphogenetic protein (BMP) exhibits a broad spectrum of biological activities in various tissues including angiogenesis. Here, this study aimed to investigate the mechanism of BMP2 in HCC by mediating the mitogen-activated protein kinase (MAPK)/p38 signaling pathway. Methods BMP2 expression was quantified in HCC and adjacent tissues. BMP2 gain- and loss-of-function experiments were conducted by infection with lentivirus over-expressing BMP2 or expressing shRNA against BMP2. The angiogenesis was evaluated with HepG2 cells co-cultured with ECV304 cells. SB-239063 was applied to inhibit the activation of the MAPK/p38 signaling pathway so as to identify the significance of this pathway in HCC progression. Finally, in vivo experiments were conducted to identify the role of BMP2 and the MAPK/p38 signaling pathway in tumor growth and angiogenesis. Results BMP2 was highly expressed in HCC. Over-expression of BMP2 was found to accelerate cell proliferation, migration, invasion, microvascular density, and angiogenesis and decrease cell apoptosis in vitro and in vivo. BMP2 silencing exhibited inhibitory effects on HCC cell invasion and angiogenesis. The co-culture system illustrated that HepG2 cells secreted BMP2 in ECV304, and silenced BMP2 in HepG2 cells resulted in the inactivation of the MAPK/p38 signaling pathway, thus suppressing cancer progression, tumor growth, and angiogenesis in HCC. Conclusion Taken together, the key findings of this study propose that silencing of BMP2 inhibits angiogenesis and tumor growth in HCC, highlighting BMP2 silencing as a potential strategy for the treatment of HCC. |
| first_indexed | 2024-04-13T04:42:48Z |
| format | Article |
| id | doaj.art-e18253cc3601415d81389ab5486cba7b |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T04:42:48Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-e18253cc3601415d81389ab5486cba7b2022-12-22T03:01:57ZengBMCStem Cell Research & Therapy1757-65122019-08-0110111510.1186/s13287-019-1301-2BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathwayPeng-Cheng Feng0Xing-Fei Ke1Hui-Lan Kuang2Li-Li Pan3Qiang Ye4Jian-Bing Wu5Department of Oncology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Oncology, The Second Affiliated Hospital of Nanchang UniversityAbstract Background Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. Bone morphogenetic protein (BMP) exhibits a broad spectrum of biological activities in various tissues including angiogenesis. Here, this study aimed to investigate the mechanism of BMP2 in HCC by mediating the mitogen-activated protein kinase (MAPK)/p38 signaling pathway. Methods BMP2 expression was quantified in HCC and adjacent tissues. BMP2 gain- and loss-of-function experiments were conducted by infection with lentivirus over-expressing BMP2 or expressing shRNA against BMP2. The angiogenesis was evaluated with HepG2 cells co-cultured with ECV304 cells. SB-239063 was applied to inhibit the activation of the MAPK/p38 signaling pathway so as to identify the significance of this pathway in HCC progression. Finally, in vivo experiments were conducted to identify the role of BMP2 and the MAPK/p38 signaling pathway in tumor growth and angiogenesis. Results BMP2 was highly expressed in HCC. Over-expression of BMP2 was found to accelerate cell proliferation, migration, invasion, microvascular density, and angiogenesis and decrease cell apoptosis in vitro and in vivo. BMP2 silencing exhibited inhibitory effects on HCC cell invasion and angiogenesis. The co-culture system illustrated that HepG2 cells secreted BMP2 in ECV304, and silenced BMP2 in HepG2 cells resulted in the inactivation of the MAPK/p38 signaling pathway, thus suppressing cancer progression, tumor growth, and angiogenesis in HCC. Conclusion Taken together, the key findings of this study propose that silencing of BMP2 inhibits angiogenesis and tumor growth in HCC, highlighting BMP2 silencing as a potential strategy for the treatment of HCC.http://link.springer.com/article/10.1186/s13287-019-1301-2BMP2MAPK/p38 signaling pathwayTumor growthAngiogenesisHepatocellular carcinoma |
| spellingShingle | Peng-Cheng Feng Xing-Fei Ke Hui-Lan Kuang Li-Li Pan Qiang Ye Jian-Bing Wu BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway Stem Cell Research & Therapy BMP2 MAPK/p38 signaling pathway Tumor growth Angiogenesis Hepatocellular carcinoma |
| title | BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway |
| title_full | BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway |
| title_fullStr | BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway |
| title_full_unstemmed | BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway |
| title_short | BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway |
| title_sort | bmp2 secretion from hepatocellular carcinoma cell hepg2 enhances angiogenesis and tumor growth in endothelial cells via activation of the mapk p38 signaling pathway |
| topic | BMP2 MAPK/p38 signaling pathway Tumor growth Angiogenesis Hepatocellular carcinoma |
| url | http://link.springer.com/article/10.1186/s13287-019-1301-2 |
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