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Lymphoma angiogenesis is orchestrated by noncanonical signaling pathways

Item Type:Article
Title:Lymphoma angiogenesis is orchestrated by noncanonical signaling pathways
Creators Name:Gloger, M. and Menzel, L. and Grau, M. and Vion, A.C. and Anagnostopoulos, I. and Zapukhlyak, M. and Gerlach, K. and Kammertöns, T. and Hehlgans, T. and Zschummel, M. and Lenz, G. and Gerhardt, H. and Höpken, U.E. and Rehm, A.
Abstract:Tumor-induced remodeling of the microenvironment relies on the formation of blood vessels, which go beyond the regulation of metabolism, shaping a maladapted survival niche for tumor cells. In high-grade B-cell lymphoma, angiogenesis correlates with poor prognosis, but attempts to target established pro-angiogenic pathways within the vascular niche have been inefficient. Here, we analyzed Myc-driven B-cell lymphoma-induced angiogenesis in mice. A few lymphoma cells were sufficient to activate the angiogenic switch in lymph nodes. A unique morphology of dense microvessels emerged without obvious tip cell guidance and reliant on blood endothelial cell (BEC) proliferation. The transcriptional response of BECs was inflammation-independent. Conventional HIF-1α or Notch signaling routes prevalent in solid tumors were not activated. Instead, a nonconventional hypersprouting morphology was orchestrated by lymphoma-provided vascular endothelial growth factor (VEGF)-C and lymphotoxin (LT). Interference with VEGF receptor-3 and LTβ receptor signaling pathways abrogated lymphoma angiogenesis, thus revealing targets to block lymphomagenesis.
Keywords:Animal Disease Models, Biopsy, Cell Proliferation, Gene Expression Profiling, Human Umbilical Vein Endothelial Cells, Indoles, Lymph Nodes, Lymphoma, Lymphotoxin beta Receptor, Lymphotoxin-alpha, Naphthalenes, Naphthyridines, Pathologic Neovascularization, Signal Transduction, Transgenic Mice, Tumor Cell Line, Tumor Microenvironment, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor Receptor-3, Xenograft Model Antitumor Assays, Animals, Mice
Source:Cancer Research
ISSN:0008-5472
Publisher:American Association for Cancer Research
Volume:80
Number:6
Page Range:1316-1329
Date:March 2020
Official Publication:https://doi.org/10.1158/0008-5472.CAN-19-1493
PubMed:View item in PubMed

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