VEGF Targets the Tumour Cell

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2013 Nov 23

PMID 24263190

Citations 588

Authors

Hira Lal Goel

Arthur M Mercurio

Affiliations

Soon will be listed here.

Abstract

The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches.

Citing Articles

One Month of Brief Weekly Magnetic Field Therapy Enhances the Anticancer Potential of Female Human Sera: Randomized Double-Blind Pilot Study.

Iversen J, Tai Y, Yap J, Abdul Razar R, Sukumar V, Wu K Cells. 2025; 14(5).

PMID: 40072060 PMC: 11899448. DOI: 10.3390/cells14050331.

Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy.

Jiao J, Wu Y, Wu S, Jiang J Curr Treat Options Oncol. 2025; .

PMID: 40045029 DOI: 10.1007/s11864-025-01306-8.

Targeting the PI3K/AKT/mTOR pathway in lung cancer: mechanisms and therapeutic targeting.

Qiang M, Chen Z, Liu H, Dong J, Gong K, Zhang X Front Pharmacol. 2025; 16:1516583.

PMID: 40041495 PMC: 11877449. DOI: 10.3389/fphar.2025.1516583.

Design of a fragment crystallizable-engineered tetravalent bispecific antibody targeting programmed cell death-1 and vascular endothelial growth factor with cooperative biological effects.

Zhong T, Zhang L, Huang Z, Pang X, Jin C, Liu W iScience. 2025; 28(3):111722.

PMID: 40034861 PMC: 11872405. DOI: 10.1016/j.isci.2024.111722.

Immunogenic cell death signature predicts survival and reveals the role of VEGFA + Mast cells in lung adenocarcinoma.

Zhang M, Zhou G, Xu Y, Wei B, Liu Q, Zhang G Sci Rep. 2025; 15(1):7213.

PMID: 40021802 PMC: 11871002. DOI: 10.1038/s41598-025-91401-5.

References

Strizzi L, Catalano A, Vianale G, Orecchia S, Casalini A, Tassi G . Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol. 2001; 193(4):468-75. DOI: 10.1002/path.824. View

Beck B, Driessens G, Goossens S, Youssef K, Kuchnio A, Caauwe A . A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours. Nature. 2011; 478(7369):399-403. DOI: 10.1038/nature10525. View

Geretti E, van Meeteren L, Shimizu A, Dudley A, Claesson-Welsh L, Klagsbrun M . A mutated soluble neuropilin-2 B domain antagonizes vascular endothelial growth factor bioactivity and inhibits tumor progression. Mol Cancer Res. 2010; 8(8):1063-73. PMC: 2923676. DOI: 10.1158/1541-7786.MCR-10-0157. View

Nobusawa S, Stawski R, Kim Y, Nakazato Y, Ohgaki H . Amplification of the PDGFRA, KIT and KDR genes in glioblastoma: a population-based study. Neuropathology. 2011; 31(6):583-8. DOI: 10.1111/j.1440-1789.2011.01204.x. View

Shintani Y, Takashima S, Asano Y, Kato H, Liao Y, Yamazaki S . Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling. EMBO J. 2006; 25(13):3045-55. PMC: 1500974. DOI: 10.1038/sj.emboj.7601188. View

Zachary I . How neuropilin-1 regulates receptor tyrosine kinase signalling: the knowns and known unknowns. Biochem Soc Trans. 2011; 39(6):1583-91. DOI: 10.1042/BST20110697. View

Spannuth W, Nick A, Jennings N, Armaiz-Pena G, Mangala L, Danes C . Functional significance of VEGFR-2 on ovarian cancer cells. Int J Cancer. 2008; 124(5):1045-53. PMC: 2668132. DOI: 10.1002/ijc.24028. View

Witte D, Thomas A, Ali N, Carlson N, Younes M . Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma. Anticancer Res. 2002; 22(3):1463-6. View

Wedam S, Low J, Yang S, Chow C, Choyke P, Danforth D . Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol. 2006; 24(5):769-77. DOI: 10.1200/JCO.2005.03.4645. View

10.

Shibuya M . Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. J Biochem. 2012; 153(1):13-9. PMC: 3528006. DOI: 10.1093/jb/mvs136. View

11.

Neufeld G, Kessler O, Herzog Y . The interaction of Neuropilin-1 and Neuropilin-2 with tyrosine-kinase receptors for VEGF. Adv Exp Med Biol. 2003; 515:81-90. DOI: 10.1007/978-1-4615-0119-0_7. View

12.

Sato H, Takeda Y . VEGFR2 expression and relationship between tumor neovascularization and histologic characteristics in oral squamous cell carcinoma. J Oral Sci. 2009; 51(4):551-7. DOI: 10.2334/josnusd.51.551. View

13.

Straume O, Akslen L . Increased expression of VEGF-receptors (FLT-1, KDR, NRP-1) and thrombospondin-1 is associated with glomeruloid microvascular proliferation, an aggressive angiogenic phenotype, in malignant melanoma. Angiogenesis. 2004; 6(4):295-301. DOI: 10.1023/B:AGEN.0000029408.08638.aa. View

14.

Samuel S, Gaur P, Fan F, Xia L, Gray M, Dallas N . Neuropilin-2 mediated β-catenin signaling and survival in human gastro-intestinal cancer cell lines. PLoS One. 2011; 6(10):e23208. PMC: 3197582. DOI: 10.1371/journal.pone.0023208. View

15.

Wey J, Fan F, Gray M, Bauer T, McCarty M, Somcio R . Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines. Cancer. 2005; 104(2):427-38. DOI: 10.1002/cncr.21145. View

16.

Snuderl M, Batista A, Kirkpatrick N, Ruiz de Almodovar C, Riedemann L, Walsh E . Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma. Cell. 2013; 152(5):1065-76. PMC: 3587980. DOI: 10.1016/j.cell.2013.01.036. View

17.

Waldner M, Wirtz S, Jefremow A, Warntjen M, Neufert C, Atreya R . VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer. J Exp Med. 2010; 207(13):2855-68. PMC: 3005238. DOI: 10.1084/jem.20100438. View

18.

Neuchrist C, Erovic B, Handisurya A, Steiner G, Rockwell P, Gedlicka C . Vascular endothelial growth factor receptor 2 (VEGFR2) expression in squamous cell carcinomas of the head and neck. Laryngoscope. 2002; 111(10):1834-41. DOI: 10.1097/00005537-200110000-00031. View

19.

Kollermann J, Helpap B . Expression of vascular endothelial growth factor (VEGF) and VEGF receptor Flk-1 in benign, premalignant, and malignant prostate tissue. Am J Clin Pathol. 2001; 116(1):115-21. DOI: 10.1309/1LBM-6X32-JH6W-ENUD. View

20.

Gray M, Van Buren G, Dallas N, Xia L, Wang X, Yang A . Therapeutic targeting of neuropilin-2 on colorectal carcinoma cells implanted in the murine liver. J Natl Cancer Inst. 2008; 100(2):109-20. DOI: 10.1093/jnci/djm279. View