Vascular Endothelial Growth Factor: Much More Than an Angiogenesis Factor

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2010 Feb 4

PMID 20124007

Citations 42

Authors

Donald R Senger

Affiliations

Soon will be listed here.

Abstract

Vascular endothelial growth factor (VEGF) is best known as a cytokine essential for embryonic vasculogenesis and for the angiogenesis associated with various pathologies including cancer. However, VEGF also serves other functions that are less widely recognized. An early study (Berse et al., 1992) revealed widespread expression of VEGF transcripts in adult tissues devoid of ongoing neovascularization, thereby predicting additional VEGF functions distinct from angiogenesis. More recent studies have confirmed that VEGF does indeed serve multiple additional functions, including normal maintenance of endothelial and neural cell compartments. These findings have important implications for the use of VEGF antagonists and VEGF receptor antagonists in patients for which inhibition of pathological angiogenesis is the therapeutic goal.

Citing Articles

The VEGFA-Induced MAPK-AKT/PTEN/TGFβ Signal Pathway Enhances Progression and MDR in Gastric Cancer.

Fang H, Zhou Y, Bai X, Che W, Zhang W, Zhang D Genes (Basel). 2024; 15(10).

PMID: 39457390 PMC: 11507385. DOI: 10.3390/genes15101266.

Effect of topical naringenin and its combination with minoxidil on enhancing hair growth in a mouse model.

Khayoon N, Gany S, Hadi N, Al Mudhafar A J Med Life. 2024; 16(11):1685-1691.

PMID: 38406772 PMC: 10893572. DOI: 10.25122/jml-2023-0094.

CircRNA-miRNA-VEGFA: an important pathway to regulate cancer pathogenesis.

Zhang L, Zhang Y, Li X, Gao H, Chen X, Li P Front Pharmacol. 2023; 14:1049742.

PMID: 37234708 PMC: 10206052. DOI: 10.3389/fphar.2023.1049742.

A review on emerging targeted therapies for the management of metastatic colorectal cancers.

Deshmukh R, Prajapati M, Harwansh R Med Oncol. 2023; 40(6):159.

PMID: 37097307 DOI: 10.1007/s12032-023-02020-x.

Homo and Heterotypic Cellular Cross-Talk in Epithelial Ovarian Cancer Impart Pro-Tumorigenic Properties through Differential Activation of the Notch3 Pathway.

Mukherjee S, Sakpal A, Mehrotra M, Phadte P, Rekhi B, Ray P Cancers (Basel). 2022; 14(14).

PMID: 35884426 PMC: 9319742. DOI: 10.3390/cancers14143365.

References

Broeders M, Tangelder G, Slaaf D, Reneman R, oude Egbrink M . Endogenous nitric oxide protects against thromboembolism in venules but not in arterioles. Arterioscler Thromb Vasc Biol. 1998; 18(1):139-45. DOI: 10.1161/01.atv.18.1.139. View

Storkebaum E, Lambrechts D, Carmeliet P . VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays. 2004; 26(9):943-54. DOI: 10.1002/bies.20092. View

Saint-Geniez M, Maharaj A, Walshe T, Tucker B, Sekiyama E, Kurihara T . Endogenous VEGF is required for visual function: evidence for a survival role on müller cells and photoreceptors. PLoS One. 2008; 3(11):e3554. PMC: 2571983. DOI: 10.1371/journal.pone.0003554. View

Senger D, Connolly D, Van de Water L, Feder J, Dvorak H . Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res. 1990; 50(6):1774-8. View

Maharaj A, DAmore P . Roles for VEGF in the adult. Microvasc Res. 2007; 74(2-3):100-13. PMC: 2128714. DOI: 10.1016/j.mvr.2007.03.004. View

Eremina V, Jefferson J, Kowalewska J, Hochster H, Haas M, Weisstuch J . VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008; 358(11):1129-36. PMC: 3030578. DOI: 10.1056/NEJMoa0707330. View

Ferrara N . VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002; 2(10):795-803. DOI: 10.1038/nrc909. View

Morbidelli L, Chang C, Douglas J, Granger H, Ledda F, Ziche M . Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium. Am J Physiol. 1996; 270(1 Pt 2):H411-5. DOI: 10.1152/ajpheart.1996.270.1.H411. View

Leung D, Cachianes G, Kuang W, Goeddel D, Ferrara N . Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989; 246(4935):1306-9. DOI: 10.1126/science.2479986. View

10.

Baffert F, Le T, Sennino B, Thurston G, Kuo C, Hu-Lowe D . Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am J Physiol Heart Circ Physiol. 2005; 290(2):H547-59. DOI: 10.1152/ajpheart.00616.2005. View

11.

Keck P, Hauser S, Krivi G, Sanzo K, Warren T, Feder J . Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989; 246(4935):1309-12. DOI: 10.1126/science.2479987. View

12.

Lee S, Chen T, Barber C, Jordan M, Murdock J, Desai S . Autocrine VEGF signaling is required for vascular homeostasis. Cell. 2007; 130(4):691-703. PMC: 3010851. DOI: 10.1016/j.cell.2007.06.054. View

13.

Papadopoulou D, Mendrinos E, Mangioris G, Donati G, Pournaras C . Intravitreal ranibizumab may induce retinal arteriolar vasoconstriction in patients with neovascular age-related macular degeneration. Ophthalmology. 2009; 116(9):1755-61. DOI: 10.1016/j.ophtha.2009.03.017. View

14.

Berse B, Brown L, Van de Water L, Dvorak H, Senger D . Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell. 1992; 3(2):211-20. PMC: 275520. DOI: 10.1091/mbc.3.2.211. View

15.

DAmore P . Modes of FGF release in vivo and in vitro. Cancer Metastasis Rev. 1990; 9(3):227-38. DOI: 10.1007/BF00046362. View

16.

Levick J, Smaje L . An analysis of the permeability of a fenestra. Microvasc Res. 1987; 33(2):233-56. DOI: 10.1016/0026-2862(87)90020-3. View

17.

Senger D, Galli S, Dvorak A, Perruzzi C, Harvey V, Dvorak H . Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983; 219(4587):983-5. DOI: 10.1126/science.6823562. View

18.

Papapetropoulos A, Garcia-Cardena G, Madri J, Sessa W . Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest. 1998; 100(12):3131-9. PMC: 508526. DOI: 10.1172/JCI119868. View

19.

Kamba T, Tam B, Hashizume H, Haskell A, Sennino B, Mancuso M . VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2005; 290(2):H560-76. DOI: 10.1152/ajpheart.00133.2005. View

20.

van der Zee R, Murohara T, Luo Z, Zollmann F, PASSERI J, Lekutat C . Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation. 1997; 95(4):1030-7. DOI: 10.1161/01.cir.95.4.1030. View