Combination of Serum Amyloid A and C-Reactive Protein Exhibit Synergistic Effect in Angiogenesis by Inducing Inflammation and Vascular Network

• Main Authors: Dan Liu, Yonghe Chen, Yunxiu Wang, Mangjuan Lei, Lin Chen, Rongliang Liang, Zhaomin Cheng, Wen Shi, Huimin Wang, Li Lin, Lina Wang, Fujia Lin, Haibiao Lin, Wanli Liu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-12-01
• Series: Frontiers in Oncology
• Subjects: binding of C-reactive protein and serum amyloid A; inflammation; vascular network; lung cancer; promotion
• Online Access: https://www.frontiersin.org/articles/10.3389/fonc.2020.576207/full

The role of angiogenesis in tumor progression has been recognized as one of the hallmarks of cancer, but the mechanism of its action remains unclear. Inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) are proposed to play causal roles in the development of various disorders, including malignancies. Previously, we identified the complex of CRP and SAA (CRP-SAA) with diagnostic and prognostic value better than either one of them in the serum of lung cancer patients. In this study, we further explored the stimulation function of CRP-SAA on angiogenesis and inflammation. To explore possible mechanisms, microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and multi-bioinformatics analysis revealed that THP-1 and human umbilical vein endothelial cells (HUVECs) responded to SAA stimulation with upregulation of two pro-angiogenic cytokines in common, i.e., C-X-C motif ligand 6 (CXCL6) and CXCL8, which were validated by subsequent experiments in vitro. CRP had weak effects as a single stimulus, but it can efficiently potentiate the SAA induction of cytokines, which was stronger than the sum of the both (P < 0.001). The synergistical effect of the combination of CRP and SAA enhanced HUVECs transwell and constricted morphology by upregulating the pro-angiogenic genes. These results indicated that the binding of CRP and SAA acted synergistically in pro-angiogenesis by increasing inflammation and inducing vascular network.