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, Jahrgang 24, Nr. 6, 06.2015, S. 424-9.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Teichert, M, Stumpf, C, Booken, N, Wobser, M, Nashan, D, Hallermann, C, Mogler, C, Müller, CSL, Becker, JC, Moritz, RKC, Andrulis, M, Nicolay, JP, Goerdt, S, Thomas, M, Klemke, C-D, Augustin, HG & Felcht, M 2015, 'Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis', EXP DERMATOL, Jg. 24, Nr. 6, S. 424-9. https://doi.org/10.1111/exd.12688

APA

Teichert, M., Stumpf, C., Booken, N., Wobser, M., Nashan, D., Hallermann, C., Mogler, C., Müller, C. S. L., Becker, J. C., Moritz, R. K. C., Andrulis, M., Nicolay, J. P., Goerdt, S., Thomas, M., Klemke, C-D., Augustin, H. G., & Felcht, M. (2015). Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis. EXP DERMATOL, 24(6), 424-9. https://doi.org/10.1111/exd.12688

Vancouver

Bibtex

@article{032ce264187844c8a9f68750e17ef456,
title = "Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis",
abstract = "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. ",
keywords = "Angiopoietin-2/genetics, Focal Adhesion Protein-Tyrosine Kinases/metabolism, Gene Expression Regulation, Neoplastic/genetics, Humans, Integrins/metabolism, Lymphoma, B-Cell/genetics, Microvessels/pathology, Neovascularization, Pathologic/metabolism, Phosphorylation, Signal Transduction/genetics, Skin Neoplasms/blood supply",
author = "Martin Teichert and Christine Stumpf and Nina Booken and Marion Wobser and Dorothee Nashan and Christian Hallermann and Carolin Mogler and M{\"u}ller, {Cornelia S L} and Becker, {J{\"u}rgen C} and Moritz, {Rose K C} and Mindaugas Andrulis and Nicolay, {Jan P} and Sergij Goerdt and Markus Thomas and Claus-Detlev Klemke and Augustin, {Hellmut G} and Moritz Felcht",
note = "{\textcopyright} 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2015",
month = jun,
doi = "10.1111/exd.12688",
language = "English",
volume = "24",
pages = "424--9",
journal = "EXP DERMATOL",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "6",

}

RIS

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 -