Human T-cell lymphotropic virus type 1-transformed cells induce angiogenesis and establish functional gap junctions with endothelial cells

Marwan E El-Sabban; Raghida Abou Merhi; Hounaida Abi Haidar; Bertrand Arnulf; Hilda Khoury; Jihane Basbous; Julie Nijmeh; Hugues de Thé; Olivier Hermine; Ali Bazarbachi

doi:10.1182/blood.v99.9.3383

Human T-cell lymphotropic virus type 1-transformed cells induce angiogenesis and establish functional gap junctions with endothelial cells

Blood. 2002 May 1;99(9):3383-9. doi: 10.1182/blood.v99.9.3383.

Authors

Marwan E El-Sabban¹, Raghida Abou Merhi, Hounaida Abi Haidar, Bertrand Arnulf, Hilda Khoury, Jihane Basbous, Julie Nijmeh, Hugues de Thé, Olivier Hermine, Ali Bazarbachi

Affiliation

¹ Department of Human Morphology, Faculty of Medicine, American University of Beirut, Lebanon.

PMID: 11964307
DOI: 10.1182/blood.v99.9.3383

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.

MeSH terms

Aorta
Cell Adhesion
Cell Communication
Cell Line, Transformed
Endothelial Growth Factors / genetics
Endothelial Growth Factors / metabolism
Endothelium, Vascular / cytology*
Fibroblast Growth Factor 2 / genetics
Fibroblast Growth Factor 2 / metabolism
Gap Junctions / pathology*
Gene Products, tax / pharmacology
Human T-lymphotropic virus 1
Humans
Leukemia-Lymphoma, Adult T-Cell / metabolism*
Leukemia-Lymphoma, Adult T-Cell / pathology
Leukemia-Lymphoma, Adult T-Cell / physiopathology*
Lymphokines / genetics
Lymphokines / metabolism
Neovascularization, Pathologic / etiology
Neovascularization, Pathologic / virology*
RNA, Messenger / metabolism
T-Lymphocytes / metabolism
T-Lymphocytes / physiology
T-Lymphocytes / virology*
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors

Substances

Endothelial Growth Factors
Gene Products, tax
Lymphokines
RNA, Messenger
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Fibroblast Growth Factor 2