[en] Angiogenesis is a complex phenomenon likely to be under the strict control of a group of transcription factor(s). Homeobox (HOX)-containing proteins have been identified as regulators controlling the coordinated expression of genes involved in organ development and tissue differentiation. In this study, we have demonstrated that human umbilical vein endothelial cells (HUVEC) express 8 of the 10 HOX genes contained in cluster B. Treatment of HUVEC with tissue plasminogen activator (TPA), an agent known to induce morphologic changes in endothelial cells, or vascular endothelium growth factor (VEGF), a proliferative and angiogenesis inducer, results in a specific time-dependent modulation of the eight HOX genes identified. Interestingly, neither basic fibroblast growth factor, an endothelial proliferative agent, nor TNP-470, a fumagillin derivative with potent antiendothelial cell proliferation properties, affected expression of these HOX genes. Specific modulation of HOX genes by differentiating agents but not by proliferative or antiproliferative molecules suggests that they could be involved in the control of the genetic program that coordinates the construction of new blood vessels.
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Malfoy, B.
Boncinelli, E.
Faiella, A.
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Language :
English
Title :
Expression and Modulation of Homeobox Genes from Cluster B in Endothelial Cells
Publication date :
October 1998
Journal title :
Laboratory Investigation
ISSN :
0023-6837
eISSN :
1530-0307
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
78
Issue :
10
Pages :
1291-9
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
ARC - Actions de recherche concertées N°96/00-191
Funders :
CAC - Centre anticancéreux près l'Université de Liège asbl [BE] Association Sportive contre le Cancer F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] Télévie [BE] FWB - Fédération Wallonie-Bruxelles [BE]
Antoine N, Greimers R, De Roanne C, Kusaka M, Heinen E, Simar LJ, and Castronovo V (1994). AGM-1470, a potent angiogenesis inhibitor, prevents the entry of normal but not transformed endothelial cells into the G1 phase of the cell cycle. Cancer Res 54:2073-2076.
Belotti D, Vergani V, Drudis T, Borsotti P, Pitelli MR, Viale G, Giavazzi R, and Taraboletti G (1996). The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin Cancer Res 2:1843-1849.
Boncinelli E, Acampora D, Pannese M, D'Esposito M, Somma R, Gaudino G, Stornaiuolo A, Cafiero M, Faiella A, and Simeone A (1989). Organization of human class I homeobox genes. Genome 31:745-756.
Boncinelli E, Simeone A, Acampora D, and Mavilio F (1991). HOX gene activation by retinoic acid. Trends Genet 7:329-334.
Boncinelli E, Somma R, Acampora D, Pannese M, D'Esposito M, Faiella A, and Simeone A (1988). Organization of human homeobox genes. Hum Reprod 3:880-886.
Boudreau N, Andrews C, Srebow A, Ravanpay A, and Cheresh DA (1997). Induction of the angiogenic phenotype by Hox D3. J Cell Biol 139:257-264.
Care A, Testa U, Bassani A, Tritarelli E, Montesoro E, Samoggia P, Cianetti L, and Peschle C (1994). Coordinate expression and proliferative role of HOXB genes in activated adult T lymphocytes. Mol Cell Biol 14:4872-4877.
Castronovo V and Belotti D (1996). TNP-470 (AGM-1470): Mechanisms of action and early clinical development. Eur J Cancer 32A:2520-2527.
Colville-Nash PR (1992). Angiogenesis and rheumatoid arthritis: Pathogenic and therapeutic implications. Ann Rheum Dis 51:919-925.
Cornelius LA, Nehring LC, Roby JD, Parks WC, and Welgus HG (1995). Human dermal microvascular endothelial cells produce matrix metalloproteinases in response to angiogenic factors and migration. J Invest Dermatol 105:170-176.
Deguchi Y, Moroney JF, and Kehrl JH (1991). Expression of the HOX-2.3 homeobox gene in human lymphocytes and lymphoid tissues. Blood 78:445-450.
Dressier GR (1989). An update on the vertebrate homeobox. Trends Genet 5:129-131.
Dvorak HF, Brown LF, Detmar M, and Dvorak AM (1995). Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029-1039.
Dvorak HF, Nagy JA, and Dvorak AM (1991). Structure of solid tumors and their vasculature: Implications for therapy with monoclonal antibodies. Cancer Cell 3:77-85.
Edelman GM and Jones FS (1993). Outside and downstream of the homeobox. J Biol Chem 268:20683-20686.
Folkman J (1995). Clinical application of research in angiogenesis. J Nat Med 1:27-31.
Gajdusek C, Luo Z, and Mayberg M (1993). Basic fibroblast growth factor and transforming growth factor beta-1: Synergistic mediators of angiogenesis in vitro. J Cell Physiol 157:133-144.
Gehring WJ (1987). Homeo boxes in the study of development. Science 236:1245-1252.
Gehring WJ, Affolter M, and Burglin T (1994). Homeodomain proteins. Annu Rev Biochem 63:487-526.
Giampaolo A, Sterpetti P, Bulgarini D, Samoggia P, Pelosi E, Valtieri M, and Peschle C (1994). Key functional role and lineage-specific expression of selected HOXB genes in purified hematopoietic progenitor differentiation. Blood 84:3637-3647.
Goto F, Goto K, Weindel K, and Folkman J (1993). Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. Lab Invest 69:508-517.
Gross JL, Moscatelli D, Jaffe EA, and Rifkin DB (1982). Plasminogen activator and collagenase production by cultured capillary endothelial cells. J Cell Biol 95:974-981.
Ingber DE and Folkman J (1989). Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: Role of extracellular matrix. J Cell Biol 109:317-330.
Jaffe EA, Nachman RL, Becker CG, and Minick CR (1973). Culture of human endothelial cells derived from umbilical veins: Identification by morphologic and immunologic criteria. J Clin Invest 52:2745-2756.
Jaynes JB and O'Farrell PH (1988). Activation and repression of transcription by homoeodomain-containing proteins that bind a common site. Nature 336:744-749.
Kongsuwan K, Webb E, Housiaux P, and Adams JM (1988). Expression of multiple homeobox genes within diverse mammalian haemopoietic lineages. EMBO J 7:2131-2138.
Krasnow MA, Saffman EE, Kornfeld K, and Hogness DS (1989). Transcriptional activation and repression by Ultrabithorax proteins in cultured Drosophila cells. Cell 57:1031-1043.
Lawrence HJ and Largman C (1992). Homeobox genes in normal hematopoiesis and leukemia. Blood 80:2445-2453.
Lawrence HJ, Stage KM, Mathews CH, Detmer K, Scibienski R, MacKenzie M, Migliaccio E, Boncinelli E, and Largman C (1993). Expression of HOX C homeobox genes in lymphoid cells. Cell Growth Differ 4:665-669.
Lewalle JM, Munaut C, Pichot B, Cataldo D, Baramova E, and Foidart JM (1995). Plasma membrane-dependent activation of gelatinase A in human vascular endothelial cells. J Cell Physiol 165:475-483.
Lill MC, Fuller JF, Herzig R, Crooks GM, and Gasson JC (1995). The role of the homeobox gene, HOX B7, in human myelomonocytic differentiation. Blood 85:692-697.
Magli MC, Barba P, Celetti A, De Vita G, Cillo C, and Boncinelli E (1991). Coordinate regulation of HOX genes in human hematopoietic cells. Proc Natl Acad Sci USA 88: 6348-6352.
Mansbridge JN, Grymes RA, and Karasek MA (1992). Modification of proto-oncogene expression by phorbol esters in human dermal microvascular endothelial cells. Cell Mol Biol (Noisy-le-grand) 38:791-798.
Mathews CH, Detmer K, Boncinelli E, Lawrence HJ, and Largman C (1991). Erythroid-restricted expression of homeobox genes of the human HOX 2 locus. Blood 78:2248-2252.
Montesano R and Orci L (1987). Phorbol esters induce angiogenesis in vitro from large-vessel endothelial cells. J Cell Physiol 130:284-291.
Montesano R, Vassalli JD, Baird A, Guillemin R, and Orci L (1986). Basic fibroblast growth factor induces angiogenesis in vitro. Proc Natl Acad Sci USA 83:7297-7301.
Moretti P, Simmons P, Thomas P, Haylock D, Rathjen P, Vadas M, and D'Andrea R (1994). Identification of homeobox genes expressed in human haemopoietic progenitor cells. Gene 144:213-219.
Moscatelli D, Jaffe E, and Rifkin DB (1980). Tetradecanoyl phorbol acetate stimulates latent collagenase production by cultured human endothelial cells. Cell 20:343-351.
Nguyen V, Schonthal A, and Feldman ST (1994). Expression of c-jun proto-oncogene in corneal endothelium. Exp Eye Res 59:335-341.
Ohkuma Y, Horikoshi M, Roeder RG, and Desplan C (1990). Binding site-dependent direct activation and repression of in vitro transcription by Drosophila homeodomain proteins. Cell 61:475-484.
Pardanaud L, Yassine F, and Dieterlen-Lievre F (1989). Relationship between vasculogenesis, angiogenesis and haemopoiesis during avian ontogeny. Development 105:473-485.
Patz A (1980). Studies on retinal neovascularization. Friedenwald Lecture. Invest Opthalmol Vis Sci 19:1133-1138.
Pepper MS, Ferrara N, Orci L, and Montesano R (1992). Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun 189:824-831.
Quaranta MT, Petrini M, Tritarelli E, Samoggia P, Care A, Bottero L, Testa U, and Peschle C (1996). HOXB cluster genes in activated natural killer lymphocytes: Expression from 3′→5′ cluster side and proliferative function. J Immunol 157:2462-2469.
Risau W (1997). Mechanisms of angiogenesis. Nature 386: 671-674.
Scott MP (1992). Vertebrate homeobox gene nomenclature (letter). Cell 71:551-553.
Scott MP, Tamkun JW, and Hartzell GWD (1989). The structure and function of the homeodomain. Biochim Biophys Acta 989:25-48.
Shen WF, Detmer K, Mathews CH, Hack FM, Morgan DA, Largman C, and Lawrence HJ (1992). Modulation of homeobox gene expression alters the phenotype of human hematopoietic cell lines. EMBO J 11:983-989.
Shen WF, Detmer K, Simonitch-Eason TA, Lawrence HJ, and Largman C (1991). Alternative splicing of the HOX 2.2 homeobox gene in human hematopoietic cells and murine embryonic and adult tissues. Nucleic Acids Res 19:539-545.
Shen WF, Largman C, Lowney P, Corral JC, Detmer K, Hauser CA, Simonitch TA, Hack FM, and Lawrence HJ (1989). Lineage-restricted expression of homeobox-containing genes in human hematopoietic cell lines. Proc Natl Acad Sci USA 86:8536-8540.
Simeone A, Acampora D, Nigro V, Faiella A, D'Esposito M, Stornaiuolo A, Mavilio F, and Boncinelli E (1991). Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells. Mech Dev 33:215-228.
Takehara K, LeRoy EC, and Grotendorst GR (1987). TGF-beta inhibition of endothelial cell proliferation: Alteration of EGF binding and EGF-induced growth-regulatory (competence) gene expression. Cell 49:415-422.
Wernert N, Raes MB, Lassalle P, Dehouck MP, Gosselin B, Vandenbunder B, and Stehelin D (1992). c-ets1 proto-oncogene is a transcription factor expressed in endothelial cells during tumor vascularization and other forms of angiogenesis in humans. Am J Pathol 140:119-127.
Wolf JEJ (1989). Angiogenesis in normal and psoriatic skin. Lab Invest 61:139-142.
