Role of PFKFB3 and CD163 in Oral Squamous Cell Carcinoma Angiogenesis
Role of PFKFB3 and CD163 in Oral Squamous Cell Carcinoma Angiogenesis
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PFKFB3 和 CD163 在口腔鳞状细胞癌血管生成中的作用
DOI：
10.1007/s11596-019-2051-1
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发表时间：
2019-06-01
影响因子：
2.4
通讯作者：
Hu, Chuan-yu
中科院分区：
文献类型：
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作者：
Li, Ji-jia;Mao, Xiao-he;Hu, Chuan-yu
6-磷酸果糖-2-激酶/果糖- 2,6 -双磷酸酶3 （PFKFB3）是一种产生果糖2,6 -二磷酸（f - 2,6 - bp）的酶，作为激活磷酸果糖激酶-1的开关，是内皮糖酵解的关键酶，介导癌变的昼夜节律控制。此外，肿瘤相关巨噬细胞（tam）在许多癌症的进展和预后中起着重要作用。然而，PFKFB3和tam在口腔鳞状细胞癌（OSCC）中的作用和临床意义尚未阐明。本研究旨在通过组织芯片技术研究OSCC中PFKFB3表达、CD163+ tam浸润与肿瘤血管生成的关系。采用免疫组化方法研究了117例OSCC标本和56例匹配的癌旁组织的组织微阵列。与正常口腔黏膜相比，OSCC标本中PFKFB3、CD163和CD31的表达水平显著升高（P<0.05）， PFKFB与肿瘤分化、肿瘤大小显著相关（P<0.05）， CD163与OSCC组织中槟榔咀嚼习惯显著相关（P<0.05）。Pearson相关分析显示，PFKFB3与CD163、CD31均显著相关（P<0.05），而CD163与CD31显著相关（P<0.001），提示PFKFB3可能通过调节CD163+ TAMs在OSCC中的浸润，促进肿瘤进展和转移过程中的血管生成。
6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), an enzyme producing fructose 2, 6-bisphosphate (F-2, 6-BP), serves as a switch to activate phosphofructokinase-1, and is a critical enzyme for endothelial glycolysis, mediating circadian control of carcinogenesis. Also, tumor-associated macrophages (TAMs) play an important role in the progression and prognosis of numerous cancers. However, the role and clinical significance of PFKFB3 and TAMs in oral squamous cell carcinoma (OSCC) have not been elucidated. The present study was designed to investigate the correlation between PFKFB3 expression, CD163+ TAMs infiltration and tumor angiogenesis in OSCC by tissue microarray. Tissue microarrays containing 117 OSCC specimens and 56 matched paracarcinoma tissues were studied by immunohistochemistry. The expression levels of PFKFB3, CD163 and CD31 were significantly increased in OSCC specimens as compared with normal oral mucosa (P<0.05), and PFKFB was signifcantly correlated with tumor differentiation and tumor size (P<0.05), and CD163 was significantly correlated with areca nut chewing habit among OSCC tissues (P<0.05). Furthermore, Pearson’s correlation analysis revealed that PFKFB3 was signifcantly correlated with both CD163 and CD31 (P<0.05), meanwhile CD163 was signifcantly correlated with CD31 (P<0.001), suggesting PFKFB3 may promote angiogenesis in tumor progression and metastases by regulating CD163+ TAMs infiltration in OSCC.