Gloger, Marleen and Menzel, Lutz and Grau, Michael and Vion, Anne-Clemence and Anagnostopoulos, Ioannis and Zapukhlyak, Myroslav and Gerlach, Kerstin and Kammertoens, Thomas and Hehlgans, Thomas and Zschummel, Maria and Lenz, Georg and Gerhardt, Holger and Hoepken, Uta E. and Rehm, Armin (2020) Lymphoma Angiogenesis Is Orchestrated by Noncanonical Signaling Pathways. CANCER RESEARCH, 80 (6). pp. 1316-1329. ISSN 0008-5472, 1538-7445
Full text not available from this repository. (Request a copy)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 proangiogenic 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 reliance on blood endothelial cell (BEC) proliferation. The transcriptional response of BECs was inflammation independent. Conventional HIF1 alpha or Notch signaling routes prevalent in solid tumors were not activated. Instead, a nonconventional hypersprouting morphology was orchestrated by lymphoma-provided VEGFC and lymphotoxin (LT). Interference with VEGF receptor-3 and LT beta receptor signaling pathways abrogated lymphoma angiogenesis, thus revealing targets to block lymphomagenesis. Significance: In lymphoma, transcriptomes and morphogenic patterns of the vasculature are distinct from processes in inflammation and solid tumors. Instead, LTbR and VEGFR3 signaling gain leading roles and are targets for lymphomagenesis blockade.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | B-CELL-LYMPHOMA; TUMOR-GROWTH; NODE; LYMPHOTOXIN; LYMPHANGIOGENESIS; BEVACIZUMAB; RITUXIMAB; BEHAVIOR; STROMA; NICHE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 11:54 |
| Last Modified: | 29 Mar 2021 11:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44931 |
Actions (login required)
 |
View Item |
