BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma.
The angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in well-characterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34(+)CD105(+) endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34(+) endothelial cells, but not in CD3(+)CD10(+)lymphoma cells, or in CD34(+) endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34(+)CD105(+) neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105(+) neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma.
Inserm, U728, Paris, France.
Philippe
P
Ratajczak
Christophe
C
Leboeuf
Li
L
Wang
Josette
J
Brière
Irmine
I
Loisel-Ferreira
Catherine
C
Thiéblemont
Wei-Li
WL
Zhao
Anne
A
Janin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018450:Disease Progression; D018572:Disease-Free Survival; D000071063:Endoglin; D042783:Endothelial Cells / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D053208:Kaplan-Meier Estimate; D061346:Laser Capture Microdissection; D008198:Lymph Nodes / Q000098:blood supply / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D055806:Microvessels / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D010297:Paris; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000032:analysis*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics
D015703:Antigens, CD; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A