[en] Ultraviolet B and genotoxic drugs induce the expression of a vascular endothelial growth factor A (VEGF-A) splice variant (VEGF111) encoded by exons 1-4 and 8 in many cultured cells. Although not detected in a series of normal human and mouse tissue, VEGF111 expression is induced in MCF-7 xenografts in nude mice upon treatment by camptothecin. The skipping of exons that contain proteolytic cleavage sites and extracellular matrix-binding domains makes VEGF111 diffusible and resistant to proteolysis. Recombinant VEGF111 activates VEGF receptor 2 (VEGF-R2) and extracellularly regulated kinase 1/2 in human umbilical vascular endothelial cells and porcine aortic endothelial cells expressing VEGF-R2. The mitogenic and chemotactic activity and VEGF111's ability to promote vascular network formation during embyonic stem cell differentiation are similar to those of VEGF121 and 165. Tumors in nude mice formed by HEK293 cells expressing VEGF111 develop a more widespread network of numerous small vessels in the peritumoral tissue than those expressing other isoforms. Its potent angiogenic activity and remarkable resistance to proteolysis makes VEGF111 a potential adverse factor during chemotherapy but a beneficial therapeutic tool for ischemic diseases.
Mineur, Pierre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Colige, Alain ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Dubail, Johanne ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Kesteloot, Frédéric ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Voo, Stefan; Universiteit Maastricht > Cardiovascular Research Institute Maastricht
Waltenberger, Johannes; Universiteit Maastricht > Cardiovascular Research Institute Maastricht
Lapière, Charles M; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Nusgens, Betty ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Lambert, Charles ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Language :
English
Title :
Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents
Publication date :
17 December 2007
Journal title :
Journal of Cell Biology
ISSN :
0021-9525
eISSN :
1540-8140
Publisher :
Rockefeller Univ Press, New York, United States - New York
Bates, D.O., T.G. Cui, J.M. Doughty, M. Winkler, M. Sugiono, J.D. Shields, D. Peat, D. Gillatt, and S.J. Harper. 2002. VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res. 62:4123-4131.
Blaudschun, R., C. Sunderkotter, P. Brenneisen, R. Hinrichs, T. Peters, L. Schneider, Z. Razi-Wolf, N. Hunzelmann, and K. Scharffetter-Kochanek. 2002. Vascular endothelial growth factor causally contributes to the angiogenic response upon ultraviolet B irradiation in vivo. Br. J. Dermatol. 146:581-587.
Brown, L.F., K.T. Yeo, B. Berse, T.K. Yeo, D.R. Senger, H.F. Dvorak, and L. van de Water. 1992. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J. Exp. Med. 176:1375-1379.
Burchardt, M., T. Burchardt, A.G. Anastasiadis, R. Buttyan, A. de la Taille, A. Shabsigh, J. Frank, and R. Shabsigh. 2005. Application of angiogenic factors for therapy of erectile dysfunction: protein and DNA transfer of VEGF 165 into the rat penis. Urology. 66:665-670.
Caldwell, R.B., M. Bartoli, M.A. Behzadian, A.E. El-Remessy, M. Al-Shabrawey, D.H. Platt, G.I. Liou, and R.W. Caldwell. 2005. Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr. Drug Targets. 6:511-524.
Carmeliet, P., V. Ferreira, G. Breier, S. Pollefeyt, L. Kieckens, M. Gertsenstein, M. Fahrig, A. Vandenhoeck, K. Harpal, C. Eberhardt, et al. 1996. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 380:435-439.
Chirgwin, J.M., A.E. Przybyla, R.J. MacDonald, and W.J. Rutter. 1979. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 18:5294-5299.
Claffey, K.P., D.R. Senger, and B.M. Spiegelman. 1995. Structural requirements for dimerization, glycosylation, secretion, and biological function of VPF/VEGF. Biochim. Biophys. Acta. 1246:1-9.
Colige, A., F. Ruggiero, I. Vandenberghe, J. Dubail, F. Kesteloot, J. Van Beeumen, A. Beschin, L. Brys, C.M. Lapiere, and B. Nusgens. 2005. Domains and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I-III and V. J. Biol. Chem. 280:34397-34408.
Deroanne, C.F., K. Bonjean, S. Servotte, L. Devy, A. Colige, N. Clausse, S. Blacher, E. Verdin, J.M. Foidart, B.V. Nusgens, and V. Castronovo. 2002. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene. 21:427-436.
Dvorak, H.F. 2000. VPF/VEGF and the angiogenic response. Semin. Perinatol. 24:75-78.
Ferrara, N. 2005. VEGF as a therapeutic target in cancer. Oncology. 69:11-16.
Ferrara, N., K. Carver-Moore, H. Chen, M. Dowd, L. Lu, K.S. O'Shea, L. Powell-Braxton, K.J. Hillan, and M.W. Moore. 1996. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 380:439-442.
Hajitou, A., N.E. Sounni, L. Devy, C. Grignet-Debrus, J.M. Lewalle, H. Li, C.F. Deroanne, H. Lu, A. Colige, and B.V. Nusgens, et al. 2001. Down-regulation of vascular endothelial growth factor by tissue inhibitor of metalloproteinase-2: effect on in vivo mammary tumor growth and angiogenesis. Cancer Res. 61:3450-3457.
Hattori-Nakakuki, Y., C. Nishigori, K. Okamoto, S. Imamura, H. Hiai, and S. Toyokuni. 1994. Formation of 8-hydroxy-2′-deoxyguanosine in epidermis of hairless mice exposed to near-UV. Biochem. Biophys. Res. Commun. 201:1132-1139.
Houck, K.A., N. Ferrara, J. Winer, G. Cachianes, B. Li, and D.W. Leung. 1991. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol. Endocrinol. 5:1806-1814.
Jingjing, L., Y. Xue, N. Agarwal, and R.S. Roque. 1999. Human Muller cells express VEGF183, a novel spliced variant of vascular endothelial growth factor. Invest. Ophthalmol. Vis. Sci. 40:752-759.
Katiyar, S.K., B.M. Bergamo, P.K. Vyalil, and C.A. Elmets. 2001. Green tea polyphenols: DNA photodamage and photoimmunology. J. Photochem. Photobiol. B. 65:109-114.
Keyt, B.A., L.T. Berleau, H.V. Nguyen, H. Chen, H. Heinsohn, R. Vandlen, and N. Ferrara. 1996. The carboxyl-terminal domain (111-165) of vascular endothelial growth factor is critical for its mitogenic potency. J. Biol. Chem. 271:7788-7795.
Lambert, C.A., A.C. Colige, C. Munaut, C.M. Lapiere, and B.V. Nusgens. 2001. Distinct pathways in the over-expression of matrix metalloproteinases in human fibroblasts by relaxation of mechanical tension. Matrix Biol. 20:397-408.
Lauer, G., S. Sollberg, M. Cole, I. Flamme, J. Sturzebecher, K. Mann, T. Krieg, and S.A. Eming. 2000. Expression and proteolysis of vascular endothelial growth factor is increased in chronic wounds. J. Invest. Dermatol. 115:12-18.
Lauer, G., S. Sollberg, M. Cole, T. Krieg, and S.A. Eming. 2002. Generation of a novel proteolysis resistant vascular endothelial growth factor165 variant by a site-directed mutation at the plasmin sensitive cleavage site. FEBS Lett. 531:309-313.
Lee, S., S.M. Jilani, G.V. Nikolova, D. Carpizo, and M.L. Iruela-Arispe. 2005. Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J. Cell Biol. 169:681-691.
Maity, A., N. Pore, J. Lee, D. Solomon, and D.M. O'Rourke. 2000. Epidermal growth factor receptor transcriptionally up-regulates vascular endothelial growth factor expression in human glioblastoma cells via a pathway involving phosphatidylinositol 3′-kinase and distinct from that induced by hypoxia. Cancer Res. 60:5879-5886.
Mineur, P., A. Guignandon, C.A. Lambert, M. Amblard, C.M. Lapiere, and B.V. Nusgens. 2005. RGDS and DGEA-induced [Ca2+]i signalling in human dermal fibroblasts. Biochim. Biophys. Acta. 1746:28-37.
Park, J.E., G.A. Keller, and N. Ferrara. 1993. The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol. Biol. Cell. 4:1317-1326.
Peretz, D., H. Gitay-Goren, M. Safran, N. Kimmel, D. Gospodarowicz, and G. Neufeld. 1992. Glycosylation of vascular endothelial growth factor is not required for its mitogenic activity. Biochem. Biophys. Res. Commun. 182:1340-1347.
Robinson, C.J., and S.E. Stringer. 2001. The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J. Cell Sci. 114:853-865.
Roth, D., M. Piekarek, M. Paulsson, H. Christ, T. Krieg, W. Bloch, J.M. Davidson, and S.A. Eming. 2006. Plasmin modulates vascular endothelial growth factor-A-mediated angiogenesis during wound repair. Am. J. Pathol. 168:670-684.
Skobe, M., P. Rockwell, N. Goldstein, S. Vosseler, and N.E. Fusenig. 1997. Halting angiogenesis suppresses carcinoma cell invasion. Nat. Med. 3:1222-1227.
Soker, S., S. Gollamudi-Payne, H. Fidder, H. Charmahelli, and M. Klagsbrun. 1997. Inhibition of vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation by a peptide corresponding to the exon 7-encoded domain of VEGF165. J. Biol. Chem. 272:31582-31588.
Soker, S., S. Takashima, H.Q. Miao, G. Neufeld, and M. Klagsbrun. 1998. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 92:735-745.
Sounni, N.E., L. Devy, A. Hajitou, F. Frankenne, C. Munaut, C. Gilles, C. Deroanne, E.W. Thompson, J.M. Foidart, and A. Noel. 2002. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression. FASEB J. 16:555-564.
Stadler, N., J. Eggermann, S. Voo, A. Kranz, and J. Waltenberger. 2007. Smoking-induced monocyte dysfunction is reversed by vitamin C supplementation in vivo. Arterioscler. Thromb. Vasc. Biol. 27:120-126.
Stein, I., M. Neeman, D. Shweiki, A. Itin, and E. Keshet. 1995. Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes. Mol. Cell. Biol. 15:5363-5368.
von Wronski, M.A., N. Raju, R. Pillai, N.J. Bogdan, E.R. Marinelli, P. Nanjappan, K. Ramalingam, T. Arunachalam, S. Eaton, K.E. Linder, et al. 2006. Tuftsin binds neuropilin-1 through a sequence similar to that encoded by exon 8 of vascular endothelial growth factor. J. Biol. Chem. 281:5702-5710.
Waltenberger, J., L. Claesson-Welsh, A. Siegbahn, M. Shibuya, and C.H. Heldin. 1994. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J. Biol. Chem. 269:26988-26995.
Whittle, C., K. Gillespie, R. Harrison, P.W. Mathieson, and S. Harper. 1999. Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant. Clin. Sci. (Lond.). 97:303-312.
Yoon, Y.S., I.A. Johnson, J.S. Park, L. Diaz, and D.W. Losordo. 2004. Therapeutic myocardial angiogenesis with vascular endothelial growth factors. Mol. Cell. Biochem. 264:63-74.
Zeng, G., S.M. Taylor, J.R. McColm, N.C. Kappas, J.B. Kearney, L.H. Williams, M.E. Hartnett, and V.L. Bautch. 2007. Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation. Blood. 109:1345-1352.
