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

• Ali Bazarbachi

  1Department of Internal Medicine,

• Raghida Abou Merhi

  1Department of Internal Medicine,

• Antoine Gessain

  2Unité d’Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France;

• Rabih Talhouk

  3Department of Biology,

• Hilda El-Khoury

  4Department of Human Morphology, and

• Rihab Nasr

  1Department of Internal Medicine,

• Olivier Gout

  5Fondation Rotschild, Paris, France;

• Rita Sulahian

  3Department of Biology,

• Fadia Homaidan

  6Department of Physiology, American University of Beirut, Lebanon;

• Hugues de Thé

  7Unité Propre de Recherche 9051, Centre National de la Recherche Scientifique, Laboratoire associé No. 11 du comité de Paris de la Ligue contre le Cancer, conventionné par l’Université Paris VII, Hôpital St. Louis, Paris, France;

• Olivier Hermine

  8Department of Clinical Hematology, Necker Hospital, Paris, France

• Marwan E. El-Sabban

  4Department of Human Morphology, and

抄録

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.

収録刊行物

• Cancer Research

  Cancer Research 64 (6), 2039-2046, 2004-03-15

  American Association for Cancer Research (AACR)

キーワード

• Cancer Research
• Oncology

詳細情報

• CRID: 1361699994769719296
• NII論文ID: 30018589757
• DOI: 10.1158/0008-5472.can-03-2390
• ISSN: 15387445
• ISSN: 00085472
• Web Site: https://aacrjournals.org/cancerres/article-pdf/64/6/2039/2523806/zch00604002039.pdf
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  • CiNii Articles