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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3383-3389
NEOPLASIA
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, and
Ali Bazarbachi
From the Departments of Human Morphology, Internal
Medicine, and Biochemistry, Faculty of Medicine, American University of
Beirut, Lebanon; CNRS UMR 8603, Necker Hospital, Paris; and CNRS UPR
9051, Hôpital St Louis, Paris, France.
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.
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