BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway (Retracted article. See vol. 13, 2022)
BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway (Retracted article. See vol. 13, 2022)
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DOI：
10.1186/s13287-019-1301-2
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发表时间：
2019-08-06
影响因子：
7.5
通讯作者：
Wu, Jian-Bing
中科院分区：
文献类型：
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作者：
Feng, Peng-Cheng;Ke, Xing-Fei;Wu, Jian-Bing
背景 肝细胞癌 (HCC) 是全球最常见的肿瘤之一，其患病率因地方性危险因素而异。骨形态发生蛋白 (BMP) 在各种组织中表现出广泛的生物活性，包括血管生成。本研究旨在探讨 BMP2 通过介导丝裂原激活蛋白激酶 (MAPK)/p38 信号通路在 HCC 中的作用机制。方法 对 HCC 和癌旁组织中的 BMP2 表达进行定量。通过感染过表达BMP2或表达针对BMP2的shRNA的慢病毒来进行BMP2功能获得和丧失实验。用与ECV304细胞共培养的HepG2细胞评估血管生成。应用SB-239063抑制MAPK/p38信号通路的激活，以确定该通路在HCC进展中的重要性。最后，进行体内实验以确定BMP2和MAPK/p38信号通路在肿瘤生长和血管生成中的作用。结果BMP2在HCC中高表达。研究发现，BMP2 的过度表达可加速细胞增殖、迁移、侵袭、微血管密度和血管生成，并在体外和体内减少细胞凋亡。 BMP2沉默对HCC细胞侵袭和血管生成具有抑制作用。共培养系统表明，HepG2细胞在ECV304中分泌BMP2，并且沉默HepG2细胞中的BMP2导致MAPK/p38信号通路失活，从而抑制HCC中的癌症进展、肿瘤生长和血管生成。结论 总而言之，本研究的主要发现表明，BMP2 沉默可抑制 HCC 中的血管生成和肿瘤生长，强调 BMP2 沉默是治疗 HCC 的潜在策略。
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.