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.
- 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.
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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