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Human T-Cell Lymphotropic Virus Type I-Infected Cells Extravasate through the Endothelial Barrier by a Local Angiogenesis-Like Mechanism

Show simple item record Bazarbachi A. Merhi R.A. Gessain A. Talhouk R. El-Khoury H. Nasr R. Gout O. Sulahian R. Homaidan F. De The H. Hermine O. El-Sabhan M.E.
dc.contributor.editor Mar-2004 2017-10-05T15:37:37Z 2017-10-05T15:37:37Z 2004
dc.identifier 10.1158/0008-5472.CAN-03-2390
dc.identifier.issn 00085472
dc.description.abstract Extravasation of tumor cells through the endothelial barrier is a critical step in cancer metastasis. Human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia-lymphoma (ATL) is an aggressive disease characterized by visceral invasion. We show that ATL and HTLV-I-associated myelopathy patients exhibit high plasma levels of functional vascular endothelial growth factor and basic fibroblast growth factor. The viral oncoprotein Tax transactivates the promoter of the gap-junction protein connexin-43 and enhances gap-junction-mediated heterocellular communication with endothelial cells. The interaction of HTLV-I-transformed cells with endothelial cells induces the gelatinase activity of matrix metalloproteinase (MMP)-2 and MMP-9 in endothelial cells and down-regulates the tissue inhibitor of MMP. This leads to subendothelial basement membrane degradation followed by endothelial cell retraction, allowing neoplastic lymphocyte extravasation. We propose a model that offers a mechanistic explanation for extravasation of HTLV-I-infected cells: after specific adhesion to endothelia of target organs, tumor cells induce a local and transient angiogenesis-like mechanism through paracrine stimulation and direct cell-cell communication with endothelial cells. This culminates in a breach of the endothelial barrier function, allowing cancer cell invasion. This local and transient angiogenesis-like sequence that may facilitate visceral invasion in ATL represents a potential target for ATL therapy.
dc.format.extent Pages: (2039-2046)
dc.language English
dc.publisher PHILADELPHIA
dc.relation.ispartof Publication Name: Cancer Research; Publication Year: 2004; Volume: 64; no. 6; Pages: (2039-2046);
dc.source Scopus
dc.title Human T-Cell Lymphotropic Virus Type I-Infected Cells Extravasate through the Endothelial Barrier by a Local Angiogenesis-Like Mechanism
dc.type Article
dc.contributor.affiliation Bazarbachi, A., Department of Internal Medicine, American University of Beirut, Beirut, Lebanon, Department of Internal Medicine, Faculty of Medicine, American University of Beirut, P.O. Box 113-6044, Beirut, Lebanon
dc.contributor.affiliation Merhi, R.A., Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Gessain, A., U. d'Epidemiol.-Physiopathol. V. O., Institut Pasteur, Paris, France
dc.contributor.affiliation Talhouk, R., Department of Biology, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation El-Khoury, H., Department of Human Morphology, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Nasr, R., Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Gout, O., Fondation Rotschild, Paris, France
dc.contributor.affiliation Sulahian, R., Department of Biology, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Homaidan, F., Department of Physiology, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation De Thé, H., Unite Propre de Recherche 9051, Ctr. Natl. de la Rech. Scientifique, Université Paris VII, Paris, France
dc.contributor.affiliation Hermine, O., Department of Clinical Hematology, Necker Hospital, Paris, France
dc.contributor.affiliation El-Sabhan, M.E., Department of Human Morphology, American University of Beirut, Beirut, Lebanon, Department of Human Morphologym, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon
dc.contributor.authorAddress Bazarbachi, A.; Department of Internal Medicine, Faculty of Medicine, American University of Beirut, P.O. Box 113-6044, Beirut, Lebanon; email:
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Internal Medicine;
dc.contributor.authorDepartment Internal Medicine
dc.contributor.faculty Faculty of Medicine
dc.contributor.authorInitials Bazarbachi, A
dc.contributor.authorInitials Merhi, RA
dc.contributor.authorInitials Gessain, A
dc.contributor.authorInitials Talhouk, R
dc.contributor.authorInitials El-Khoury, H
dc.contributor.authorInitials Nasr, R
dc.contributor.authorInitials Gout, O
dc.contributor.authorInitials Sulahian, R
dc.contributor.authorInitials Homaidan, F
dc.contributor.authorInitials de The, H
dc.contributor.authorInitials Hermine, O
dc.contributor.authorInitials El-Sabban, ME
dc.contributor.authorReprintAddress El-Sabban, ME (reprint author), Amer Univ Beirut, Fac Med, Dept Human Morphol, POB 11-0236, Beirut, Lebanon.
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 32
dc.description.citedTotWOSCount 30
dc.description.citedWOSCount 27
dc.format.extentCount 8
dc.identifier.coden CNREA
dc.identifier.pubmedID 15026341
dc.identifier.scopusID 12144290035
dc.publisher.address 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
dc.relation.ispartOfISOAbbr Cancer Res.
dc.relation.ispartOfIssue 6
dc.relation.ispartofPubTitle Cancer Research
dc.relation.ispartofPubTitleAbbr Cancer Res.
dc.relation.ispartOfVolume 64
dc.source.ID WOS:000220249100023
dc.type.publication Journal
dc.subject.otherChemCAS basic fibroblast growth factor, 106096-93-9
dc.subject.otherChemCAS gelatinase A, 146480-35-5
dc.subject.otherChemCAS gelatinase B, 146480-36-6
dc.subject.otherChemCAS vasculotropin, 127464-60-2
dc.subject.otherChemCAS Connexin 43
dc.subject.otherChemCAS Fibroblast Growth Factor 2, 103107-01-3
dc.subject.otherChemCAS Matrix Metalloproteinase 2, EC
dc.subject.otherChemCAS Matrix Metalloproteinase 9, EC
dc.subject.otherChemCAS RNA, Messenger
dc.subject.otherChemCAS Tissue Inhibitor of Metalloproteinases
dc.subject.otherChemCAS Vascular Endothelial Growth Factor A
dc.subject.otherIndex basic fibroblast growth factor
dc.subject.otherIndex connexin 43
dc.subject.otherIndex gelatinase A
dc.subject.otherIndex gelatinase B
dc.subject.otherIndex Tax protein
dc.subject.otherIndex vasculotropin
dc.subject.otherIndex angiogenesis
dc.subject.otherIndex article
dc.subject.otherIndex basement membrane
dc.subject.otherIndex cancer cell
dc.subject.otherIndex cancer invasion
dc.subject.otherIndex cell communication
dc.subject.otherIndex cell transformation
dc.subject.otherIndex controlled study
dc.subject.otherIndex down regulation
dc.subject.otherIndex drug targeting
dc.subject.otherIndex endothelium cell
dc.subject.otherIndex enzyme activity
dc.subject.otherIndex extravasation
dc.subject.otherIndex gap junction
dc.subject.otherIndex human
dc.subject.otherIndex human cell
dc.subject.otherIndex Human T cell leukemia virus 1
dc.subject.otherIndex metastasis
dc.subject.otherIndex paracrine signaling
dc.subject.otherIndex priority journal
dc.subject.otherIndex promoter region
dc.subject.otherIndex spinal cord disease
dc.subject.otherIndex T cell leukemia
dc.subject.otherIndex T cell lymphoma
dc.subject.otherIndex transactivation
dc.subject.otherIndex tumor cell
dc.subject.otherIndex virus infectivity
dc.subject.otherIndex virus pathogenesis
dc.subject.otherIndex CD4-Positive T-Lymphocytes
dc.subject.otherIndex Cell Adhesion
dc.subject.otherIndex Cell Communication
dc.subject.otherIndex Cell Line, Transformed
dc.subject.otherIndex Cell Transformation, Viral
dc.subject.otherIndex Connexin 43
dc.subject.otherIndex Endothelium, Vascular
dc.subject.otherIndex Fibroblast Growth Factor 2
dc.subject.otherIndex Genes, pX
dc.subject.otherIndex Human T-lymphotropic virus 1
dc.subject.otherIndex Humans
dc.subject.otherIndex Lymphoma, T-Cell
dc.subject.otherIndex Matrix Metalloproteinase 2
dc.subject.otherIndex Matrix Metalloproteinase 9
dc.subject.otherIndex Neovascularization, Pathologic
dc.subject.otherIndex RNA, Messenger
dc.subject.otherIndex Tissue Inhibitor of Metalloproteinases
dc.subject.otherIndex Tumor Cells, Cultured
dc.subject.otherIndex Vascular Endothelial Growth Factor A
dc.subject.otherKeywordPlus GROWTH-FACTOR
dc.subject.otherKeywordPlus TUMOR-CELLS
dc.subject.otherKeywordPlus MOLECULAR-MECHANISMS
dc.subject.otherKeywordPlus ORGAN-PREFERENCE
dc.subject.otherKeywordPlus CARCINOMA CELLS
dc.subject.otherKeywordPlus GAP-JUNCTIONS
dc.subject.otherKeywordPlus METASTASIS
dc.subject.otherKeywordPlus ADHESION
dc.subject.otherKeywordPlus COMMUNICATION
dc.subject.otherKeywordPlus PROGRESSION
dc.subject.otherWOS Oncology

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