Journal Article

DKFZ-2017-03631

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Aggressive primary cutaneous B-cell lymphomas show increased Angiopoietin-2-induced angiogenesis.

Teichert, M. (First author)DKFZ* ; Stumpf, C. ; Booken, N. ; Wobser, M. ; Nashan, D. ; Hallermann, C. ; Mogler, C.DKFZ* ; Müller, C. S. L. ; Becker, J.DKFZ* ; Moritz, R. K. C. ; Andrulis, M. ; Nicolay, J. P. ; Goerdt, S. ; Thomas, M. ; Klemke, C.-D. ; Augustin, H.DKFZ* ; Felcht, M. (Last author)DKFZ*

2015
Wiley-Blackwell Oxford

This record in other databases:  

Please use a persistent id in citations: doi:10.1111/exd.12688

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.

Keyword(s): ANGPT2 protein, human ; Angiopoietin-2 ; Integrins ; Focal Adhesion Protein-Tyrosine Kinases

---

Contributing Institute(s):

1. Vaskuläre Onkologie und Metastasierung (A190)
2. DKTK Essen (L401)
3. DKTK Heidelberg (L101)

Research Program(s):

1. 311 - Signalling pathways, cell and tumor biology (POF3-311) (POF3-311)

Appears in the scientific report 2015

---

Database coverage:
; Current Contents - Clinical Medicine ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---