Lymphoma angiogenesis is orchestrated by noncanonical signaling pathways

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Item Type:	Article
Title:	Lymphoma angiogenesis is orchestrated by noncanonical signaling pathways
Creators Name:	Gloger, M., Menzel, L., Grau, M., Vion, A.C., Anagnostopoulos, I., Zapukhlyak, M., Gerlach, K., Kammertöns, T., Hehlgans, T., Zschummel, M., Lenz, G., Gerhardt, H., 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
Additional Information:	Copyright © 2020 American Association for Cancer Research.
Official Publication:	https://doi.org/10.1158/0008-5472.CAN-19-1493
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