Role of PFKFB3 and CD163 in Oral Squamous Cell Carcinoma Angiogenesis

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, CD 163+ 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 significantly correlated with tumor differentiation and tumor size (P<0.05), and CD 163 was significantly correlated with areca nut chewing habit among OSCC tissues (P<0.05). Furthermore, Pearson's correlation analysis revealed that PFKFB3 was significantly correlated with both CD 163 and CD31 (P<0.05), meanwhile CD 163 was significantly correlated with CD31 (P<0.001), suggesting PFKFB3 may promote angiogenesis in tumor progression and metastases by regulating CD 163+ TAMs infiltration in OSCC.