title: Human T-cell lymphotropic virus type 1-transformed cells induce angiogenesis and establish functional gap junctions with endothelial cells.
abstract: The role of angiogenesis in the growth and metastasis of solid tumors is well established. However, the role of angiogenesis in hematologic malignancies was only recently appreciated. We show that HTLV-I-transformed T cells, but not HTLV-I-negative CD4(+) T cells, secrete biologically active forms of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and, accordingly, induce angiogenesis in vitro. Furthermore, fresh ATL leukemic cells derived from patients with acute ATL produce VEGF and bFGF transcripts and proteins. The viral transactivator Tax activates the VEGF promoter, linking the induction of angiogenesis to viral gene expression. Angiogenesis is associated with the adhesion of HTLV-I-transformed cells to endothelial cells and gap junction-mediated heterocellular communication between the 2 cell types. Angiogenesis, cell adhesion, and communication likely contribute to the development of adult T-cell leukemia-lymphoma and represent potential therapeutic targets.
authors.affiliation: Department of Human Morphology, Faculty of Medicine, American University of Beirut, Lebanon.
authors.forename: Marwan E
authors.initials: ME
authors.lastname: El-Sabban
authors.forename: Raghida Abou
authors.initials: RA
authors.lastname: Merhi
authors.forename: Hounaida Abi
authors.initials: HA
authors.lastname: Haidar
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnulf
authors.forename: Hilda
authors.initials: H
authors.lastname: Khoury
authors.forename: Jihane
authors.initials: J
authors.lastname: Basbous
authors.forename: Julie
authors.initials: J
authors.lastname: Nijmeh
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
mesh_terms: D001011:Aorta; D002448:Cell Adhesion; D002450:Cell Communication; D002461:Cell Line, Transformed; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000473:pathology*; D016356:Gene Products, tax / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000821:virology*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology / Q000821:virology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D016356:Gene Products, tax; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2