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000127608 1001_ $$0P:(DE-HGF)0$$aTeichert, Martin$$b0$$eFirst author
000127608 245__ $$aAggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis.
000127608 260__ $$aOxford$$bWiley-Blackwell$$c2015
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000127608 520__ $$aPrimary cutaneous large B-cell lymphomas, leg type (PCLBCL/LT) are primary cutaneous B-cell lymphoma (PCBCL) with an intermediate prognosis. Therefore, antracycline-based polychemotherapy combined with rituximab has been recommended as first-line treatment. Yet, despite this regimen, the 5-year survival rate remains 50-66% only. Angiogenesis, the formation of a vascular network, is essential for the pathogenesis of nodal lymphomas. So far, no study has analysed angiogenesis and its key factors in PCLBCL/LT. The present study was aimed at characterizing angiogenesis in PCLBCL/LT to identify the angiogenic molecules as potential therapeutic targets. The intra-tumoral microvessel density (MVD) was assessed by immunohistochemical studies of CD20 and CD31. The MVD was higher in PCLBCL/LT compared with indolent PCBCL. Analyses of open-source microarray data showed correlation between the angiogenic molecule angiopoietin-2 (Ang-2) and pan-endothelial cell markers. ELISA studies determined a shift between Ang-2 and Ang-1 towards Ang-2 in the peripheral blood of PCLBCL/LT patients. Immunofluorescence costainings against the Ang receptor Tie2/angiogenic integrins/CD34 revealed that the vasculature in both aggressive and indolent PCBCL tumors harbours an endothelial cell subpopulation with reduced expression of Tie2. In contrast, the alternative Ang-2 binding partners, angiogenic integrins, are strongly expressed in PCBCL. In line with these findings, downstream targets of Ang-2-integrin signalling, that is phosphorylation of focal adhesion kinase at Tyr397, and sprouting angiogenesis are enhanced in PCLBCL/LT. Our data present Ang-2 as a promising therapeutic target and anti-angiogenic therapy as a new line in treatment of PCLBCL/LT as a hitherto intractable disease.
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000127608 650_7 $$2NLM Chemicals$$aANGPT2 protein, human
000127608 650_7 $$2NLM Chemicals$$aAngiopoietin-2
000127608 650_7 $$2NLM Chemicals$$aIntegrins
000127608 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$aFocal Adhesion Protein-Tyrosine Kinases
000127608 7001_ $$aStumpf, Christine$$b1
000127608 7001_ $$aBooken, Nina$$b2
000127608 7001_ $$aWobser, Marion$$b3
000127608 7001_ $$aNashan, Dorothee$$b4
000127608 7001_ $$aHallermann, Christian$$b5
000127608 7001_ $$0P:(DE-He78)18e5b355e4a312d2065b1ae2a9d47654$$aMogler, Carolin$$b6$$udkfz
000127608 7001_ $$aMüller, Cornelia S L$$b7
000127608 7001_ $$0P:(DE-He78)7bf2f090fe39a6cd6f0bccf5ea2d4fb3$$aBecker, Jürgen$$b8$$udkfz
000127608 7001_ $$aMoritz, Rose K C$$b9
000127608 7001_ $$aAndrulis, Mindaugas$$b10
000127608 7001_ $$0P:(DE-HGF)0$$aNicolay, Jan P$$b11
000127608 7001_ $$aGoerdt, Sergij$$b12
000127608 7001_ $$aThomas, Markus$$b13
000127608 7001_ $$aKlemke, Claus-Detlev$$b14
000127608 7001_ $$0P:(DE-He78)2e92d0ae281932fc7347d819fec36b0b$$aAugustin, Hellmut$$b15$$udkfz
000127608 7001_ $$0P:(DE-He78)28b708d8e88fbb959e31ff6770aaa6c7$$aFelcht, Moritz$$b16$$eLast author$$udkfz
000127608 773__ $$0PERI:(DE-600)2026228-0$$a10.1111/exd.12688$$gVol. 24, no. 6, p. 424 - 429$$n6$$p424 - 429$$tExperimental dermatology$$v24$$x0906-6705$$y2015
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