Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis
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Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis. / Teichert, Martin; Stumpf, Christine; Booken, Nina; Wobser, Marion; Nashan, Dorothee; Hallermann, Christian; Mogler, Carolin; Müller, Cornelia S L; Becker, Jürgen C; Moritz, Rose K C; Andrulis, Mindaugas; Nicolay, Jan P; Goerdt, Sergij; Thomas, Markus; Klemke, Claus-Detlev; Augustin, Hellmut G; Felcht, Moritz.
In: EXP DERMATOL, Vol. 24, No. 6, 06.2015, p. 424-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis
AU - Teichert, Martin
AU - Stumpf, Christine
AU - Booken, Nina
AU - Wobser, Marion
AU - Nashan, Dorothee
AU - Hallermann, Christian
AU - Mogler, Carolin
AU - Müller, Cornelia S L
AU - Becker, Jürgen C
AU - Moritz, Rose K C
AU - Andrulis, Mindaugas
AU - Nicolay, Jan P
AU - Goerdt, Sergij
AU - Thomas, Markus
AU - Klemke, Claus-Detlev
AU - Augustin, Hellmut G
AU - Felcht, Moritz
N1 - © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2015/6
Y1 - 2015/6
N2 - Primary cutaneous large B-cell lymphomas, leg type (PCLBCL/LT) are primary cutaneous B-cell lymphoma (PCBCL) with an intermediate prognosis. Therefore, antracycline-based polychemotherapy combined with rituximab has been recommended as first-line treatment. Yet, despite this regimen, the 5-year survival rate remains 50-66% only. Angiogenesis, the formation of a vascular network, is essential for the pathogenesis of nodal lymphomas. So far, no study has analysed angiogenesis and its key factors in PCLBCL/LT. The present study was aimed at characterizing angiogenesis in PCLBCL/LT to identify the angiogenic molecules as potential therapeutic targets. The intra-tumoral microvessel density (MVD) was assessed by immunohistochemical studies of CD20 and CD31. The MVD was higher in PCLBCL/LT compared with indolent PCBCL. Analyses of open-source microarray data showed correlation between the angiogenic molecule angiopoietin-2 (Ang-2) and pan-endothelial cell markers. ELISA studies determined a shift between Ang-2 and Ang-1 towards Ang-2 in the peripheral blood of PCLBCL/LT patients. Immunofluorescence costainings against the Ang receptor Tie2/angiogenic integrins/CD34 revealed that the vasculature in both aggressive and indolent PCBCL tumors harbours an endothelial cell subpopulation with reduced expression of Tie2. In contrast, the alternative Ang-2 binding partners, angiogenic integrins, are strongly expressed in PCBCL. In line with these findings, downstream targets of Ang-2-integrin signalling, that is phosphorylation of focal adhesion kinase at Tyr397, and sprouting angiogenesis are enhanced in PCLBCL/LT. Our data present Ang-2 as a promising therapeutic target and anti-angiogenic therapy as a new line in treatment of PCLBCL/LT as a hitherto intractable disease.
AB - Primary cutaneous large B-cell lymphomas, leg type (PCLBCL/LT) are primary cutaneous B-cell lymphoma (PCBCL) with an intermediate prognosis. Therefore, antracycline-based polychemotherapy combined with rituximab has been recommended as first-line treatment. Yet, despite this regimen, the 5-year survival rate remains 50-66% only. Angiogenesis, the formation of a vascular network, is essential for the pathogenesis of nodal lymphomas. So far, no study has analysed angiogenesis and its key factors in PCLBCL/LT. The present study was aimed at characterizing angiogenesis in PCLBCL/LT to identify the angiogenic molecules as potential therapeutic targets. The intra-tumoral microvessel density (MVD) was assessed by immunohistochemical studies of CD20 and CD31. The MVD was higher in PCLBCL/LT compared with indolent PCBCL. Analyses of open-source microarray data showed correlation between the angiogenic molecule angiopoietin-2 (Ang-2) and pan-endothelial cell markers. ELISA studies determined a shift between Ang-2 and Ang-1 towards Ang-2 in the peripheral blood of PCLBCL/LT patients. Immunofluorescence costainings against the Ang receptor Tie2/angiogenic integrins/CD34 revealed that the vasculature in both aggressive and indolent PCBCL tumors harbours an endothelial cell subpopulation with reduced expression of Tie2. In contrast, the alternative Ang-2 binding partners, angiogenic integrins, are strongly expressed in PCBCL. In line with these findings, downstream targets of Ang-2-integrin signalling, that is phosphorylation of focal adhesion kinase at Tyr397, and sprouting angiogenesis are enhanced in PCLBCL/LT. Our data present Ang-2 as a promising therapeutic target and anti-angiogenic therapy as a new line in treatment of PCLBCL/LT as a hitherto intractable disease.
KW - Angiopoietin-2/genetics
KW - Focal Adhesion Protein-Tyrosine Kinases/metabolism
KW - Gene Expression Regulation, Neoplastic/genetics
KW - Humans
KW - Integrins/metabolism
KW - Lymphoma, B-Cell/genetics
KW - Microvessels/pathology
KW - Neovascularization, Pathologic/metabolism
KW - Phosphorylation
KW - Signal Transduction/genetics
KW - Skin Neoplasms/blood supply
U2 - 10.1111/exd.12688
DO - 10.1111/exd.12688
M3 - SCORING: Journal article
C2 - 25776770
VL - 24
SP - 424
EP - 429
JO - EXP DERMATOL
JF - EXP DERMATOL
SN - 0906-6705
IS - 6
ER -