Angiogenic mediators of the angiopoietin system are highly expressed by CD10-positive lymphoma cells in angioimmunoblastic T-cell lymphoma.
Angioimmunoblastic T-cell lymphoma (AILT) is a malignant disease of peripheral T-cell origin that is characterized by a prominent proliferation of high endothelial venules in the lymph node. To investigate angiogenic mechanisms in AILT we measured the angiogenic mediator gene expression levels in the lymph nodes of 54 non-Hodgkin lymphoma patients, by immunostaining and quantitative reverse transcription polymerase chain reaction. Angiogenic mediators angiopoietin (Ang) 1 (ANGPT1), Ang2 (ANGPT2) and their receptor, Tie2 (TEK), vascular endothelial growth factor (VEGF; VEGFA) and its receptor, VEGFR2 (KDR), and hepatocyte growth factor (HGF) and its receptor, c-Met (MET) were all more highly expressed in AILT lymph nodes (16 cases) than in B-cell lymphomas (24 cases). Moreover, significantly higher Ang1 and Tie2 expression was detected in AILT cases with CD10-positive neoplastic T-cells by comparison with unspecified peripheral T-cell lymphoma (14 cases). Immunostaining confirmed the expression of Ang1 and VEGF by both neoplastic T-cells and follicular dendritic cells. These results suggest that the angiopoietin system may play an important role in the development of high vascularity in AILT lymph nodes. Consequently, as neoplastic T-cells and follicular dendritic cells are both increased in AILT and may represent an important source of angiogenic mediators, targeting these cells with anti-angiogenic strategies might represent a novel therapy for AILT.
Konstantinou
Klio
K
Department of Comprehensive Pathology, Ageing and Developmental Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Yamamoto
Kouhei
K
Ishibashi
Fumiaki
F
Mizoguchi
Yuiko
Y
Kurata
Morito
M
Nakagawa
Yasunori
Y
Suzuki
Kenshi
K
Sawabe
Motoji
M
Ohta
Masatsugu
M
Miyakoshi
Shigesaburo
S
Crawley
James T
JT
Kitagawa
Masanobu
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D042702:Angiopoietin-2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism*; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D015260:Neprilysin / Q000032:analysis; D042787:Receptor, TIE-2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042682:Angiopoietins; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D017464:Receptors, Complement 3d; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D015260:Neprilysin