1. Academic Validation
  2. PDGF-CC underlies resistance to VEGF-A inhibition and combinatorial targeting of both suppresses pathological angiogenesis more efficiently

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

  • Oncotarget. 2016 Nov 22;7(47):77902-77915. doi: 10.18632/oncotarget.12843.
Lei Zheng 1 2 Chen Zhao 3 Yuxiang Du 2 Xianchai Lin 2 Yida Jiang 2 Chunsik Lee 2 Geng Tian 1 Jia Mi 1 Xianglin Li 1 Qishan Chen 2 Zhimin Ye 2 Lijuan Huang 2 Shasha Wang 2 Xiangrong Ren 2 Liying Xing 2 Wei Chen 2 Delong Huang 1 2 Zhiqin Gao 4 Shuping Zhang 1 Weisi Lu 2 Zhongshu Tang 2 Bin Wang 5 Rong Ju 2 Xuri Li 1 2
Affiliations

Affiliations

  • 1 Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.
  • 2 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
  • 3 Department 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.
  • 4 Department of Cell Biology, Weifang Medical University, Weifang, 261053 P. R. China.
  • 5 Medical Imaging Institute, Shandong Province Characteristical Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai, 264003 P. R. China.
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.

Keywords

PDGF-CC; VEGF-A; angiogenesis; drug resistance.

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