HIF-1α及CD31促进晚期肝癌转移及侵袭的分子机制

Molecular Mechanism of HIF-1α and CD31 Promoting Metastasis and Invasion of Advanced Hepatocellular Carcinoma

摘要: 缺氧是实体肿瘤微环境(TME)的重要生物学特征，与肿瘤的侵袭转移密切相关。由于正常组织的氧供无法为肿瘤细胞提供充足的生长条件，肿瘤细胞内部会加速新生血管的形成进一步加重缺氧。低氧诱导因子(HIF-1α)被认为是在低氧条件下激活的关键转录调节因子，相关研究表明HIF-1α在肝癌组织中呈高度表达，促进血管生成及肿瘤的侵袭和转移，并维持着肿瘤细胞的代谢，是肝细胞癌发生、发展过程中重要的调控蛋白之一，与HIF-1α相关的HCC治疗也取得了快速地进展。与此同时，研究发现TME可以通过血小板内皮细胞粘附因子1 (PECAM-1/CD31)发挥作用，推动晚期转移进展，并在肿瘤进展的前终末阶段中起关键作用，且HIF-1α与CD31表达具有相关性。本综述重点总结HIF-1α及CD31促进晚期肝癌(HCC)转移及侵袭的分子机制。

Abstract: Hypoxia is an important biological feature of solid tumor microenvironment (TME), which is closely related to tumor invasion and metastasis. As normal tissue oxygen supply cannot provide sufficient growth conditions for tumor cells, the formation of new blood vessels will be accelerated inside tumor cells to further aggravate hypoxia. HIF-1α is considered under the condition of low oxygen activation key transcriptional regulation factor. Related studies have shown that HIF-1α is highly expressed in liver cancer tissue, promotes angiogenesis and tumor invasion and metastasis, and maintains the tumor cell’s metabolism, which is one of the important regulatory proteins in the occurrence and development of hepatocellular carcinoma. HIF-1α-related HCC treatment has also made rapid progress. At the same time, TME was found to play a role through platelet endothelial cell adhesion factor 1 (PECAM-1/CD31), promoting the progression of late metastasis and playing a key role in the preterminal stage of tumor progression, and hiF-1α was correlated with CD31 expression. This review focuses on the molecular mechanisms by which HIF-1α and CD31 promote metastasis and invasion of advanced hepatocellular carcinoma (HCC).