2. Academic Validation
  3. 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.
PMID: 27788490 DOI: 10.18632/oncotarget.12843
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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