title: PDGF-CC underlies resistance to VEGF-A inhibition and combinatorial targeting of both suppresses pathological angiogenesis more efficiently.
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.
authors: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.|State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Lei
authors: L
authors: Zheng
authors: 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.
authors: Chen
authors: C
authors: Zhao
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Yuxiang
authors: Y
authors: Du
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Xianchai
authors: X
authors: Lin
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Yida
authors: Y
authors: Jiang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Chunsik
authors: C
authors: Lee
authors: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.
authors: Geng
authors: G
authors: Tian
authors: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.
authors: Jia
authors: J
authors: Mi
authors: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.
authors: Xianglin
authors: X
authors: Li
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Qishan
authors: Q
authors: Chen
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Zhimin
authors: Z
authors: Ye
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Lijuan
authors: L
authors: Huang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Shasha
authors: S
authors: Wang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Xiangrong
authors: X
authors: Ren
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Liying
authors: L
authors: Xing
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Wei
authors: W
authors: Chen
authors: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.|State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Delong
authors: D
authors: Huang
authors: Department of Cell Biology, Weifang Medical University, Weifang, 261053 P. R. China.
authors: Zhiqin
authors: Z
authors: Gao
authors: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.
authors: Shuping
authors: S
authors: Zhang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Weisi
authors: W
authors: Lu
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Zhongshu
authors: Z
authors: Tang
authors: Medical Imaging Institute, Shandong Province Characteristical Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai, 264003 P. R. China.
authors: Bin
authors: B
authors: Wang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Rong
authors: R
authors: Ju
authors: Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong, 264003, P. R. China.|State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
authors: Xuri
authors: X
authors: Li
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; C411423:platelet-derived growth factor C
keywords: PDGF-CC; VEGF-A; angiogenesis; drug resistance