Journal
ONCOTARGET
Volume 7, Issue 47, Pages 77902-77915Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12843
Keywords
angiogenesis; PDGF-CC; VEGF-A; drug resistance
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Funding
- Taishan Scholar's program
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou
- Innovation Team Program of the Jiangsu Province
- National Natural Science Foundation of China [81330021, 81470644]
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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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