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

• Published in: Blood 2002-05, Vol.99 (9), p.3383-3389
• Main Authors: El-Sabban, Marwan E., Merhi, Raghida Abou, Haidar, Hounaida Abi, Arnulf, Bertrand, Khoury, Hilda, Basbous, Jihane, Nijmeh, Julie, de Thé, Hugues, Hermine, Olivier, Bazarbachi, Ali
• Format: Article
• Language: English
• Subjects: Aorta; Biological and medical sciences; 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; Hematologic and hematopoietic diseases; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell - metabolism; Leukemia-Lymphoma, Adult T-Cell - pathology; Leukemia-Lymphoma, Adult T-Cell - physiopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life Sciences; Lymphokines - genetics; Lymphokines - metabolism; Medical sciences; Microbiology and Parasitology; 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; Virology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.9.3383

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.