Oncotarget

Research Papers:

PDGF-CC underlies resistance to VEGF-A inhibition and combinatorial targeting of both suppresses pathological angiogenesis more efficiently

Lei Zheng, Chen Zhao, Yuxiang Du, Xianchai Lin, Yida Jiang, Chunsik Lee, Geng Tian, Jia Mi, Xianglin Li, Qishan Chen, Zhimin Ye, Lijuan Huang, Shasha Wang, Xiangrong Ren, Liying Xing, Wei Chen, Delong Huang, Zhiqin Gao, Shuping Zhang, Weisi Lu, Zhongshu Tang, Bin Wang, Rong Ju and Xuri Li _

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Oncotarget. 2016; 7:77902-77915. https://doi.org/10.18632/oncotarget.12843

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Abstract

Lei Zheng1,2,*, Chen Zhao3,*, Yuxiang Du2, Xianchai Lin2, Yida Jiang2, Chunsik Lee2, Geng Tian1, Jia Mi1, Xianglin Li1, Qishan Chen2, Zhimin Ye2, Lijuan Huang2, Shasha Wang2, Xiangrong Ren2, Liying Xing2, Wei Chen2, Delong Huang1,2, Zhiqin Gao4, Shuping Zhang1, Weisi Lu2, Zhongshu Tang2, Bin Wang5, Rong Ju2, Xuri Li1,2

1Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China

2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China

3Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, P. R. China

4Department of Cell Biology, Weifang Medical University, Weifang, 261053 P. R. China

5Medical Imaging Institute, Shandong Province Characteristical Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai, 264003 P. R. China

*Equal first authors

Correspondence to:

Xuri Li, email: [email protected]

Rong Ju, email: [email protected]

Bin Wang, email: [email protected]

Keywords: angiogenesis, PDGF-CC, VEGF-A, drug resistance

Received: May 11, 2016    Accepted: October 14, 2016    Published: October 24, 2016

ABSTRACT

Anti-VEGF-A therapy has proven to be effective for many neovascular diseases. However, drug resistance to anti-VEGF-A treatment can develop. Also, not all patients with neovascular diseases are responsive to anti-VEGF-A treatment. The mechanisms underlying these important issues remain unclear. In this study, using different model systems, we found that inhibition of VEGF-A directly upregulated PDGF-CC and its receptors in multiple cell types in pathological angiogenesis in vitro and in vivo. Importantly, we further revealed that combinatorial targeting of VEGF-A and PDGF-CC suppressed pathological angiogenesis more efficiently than monotherapy. Given the potent angiogenic activity of PDGF-CC, our findings suggest that the development of resistance to anti-VEGF-A treatment may be caused by the compensatory upregulation of PDGF-CC, and combined inhibition of VEGF-A and PDGF-CC may have therapeutic advantages in treating neovascular diseases.


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