Mechanisms of Tumor-Induced Lymphovascular Niche Formation in Draining Lymph Nodes

Open access
Date
2018-12-26Type
- Journal Article
Citations
Cited 35 times in
Web of Science
Cited 38 times in
Scopus
ETH Bibliography
yes
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Abstract
Enlargement of the lymphatic vascular network in tumor-draining lymph nodes (LNs) often precedes LN metastasis, likely providing a lymphovascular niche for tumor cells. We investigated morphological and molecular changes associated with the lymphatic remodeling process, using the 4T1 breast cancer and B16F10 melanoma models. Lymphatic expansion in tumor-draining LNs is mediated by sprouting and proliferation of lymphatic endothelial cells (LECs) as early as 4 days after tumor implantation. RNA sequencing revealed an altered transcriptional profile of LECs from tumor-draining compared to naive LNs with similar changes in both tumor models. Integrin αIIb is upregulated in LECs of tumor-draining LNs and mediates LEC adhesion to fibrinogen in vitro. LEC-associated fibrinogen was also detected in LNs in vivo, suggesting a role of integrin αIIb in lymphatic remodeling. Together, our results identify specific responses of LN LECs to tumor stimuli and provide insights into the mechanisms of lymphovascular niche formation in tumor-draining LNs. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000313290Publication status
publishedExternal links
Journal / series
Cell ReportsVolume
Pages / Article No.
Publisher
ElsevierSubject
breast cancer; skin cancer; tumor promotion and progression; cell adhesion; cell matrix interactions; endothelial cell functions; lymph node lymphangiogenesis; gene expression profilingOrganisational unit
02891 - ScopeM / ScopeM
03683 - Detmar, Michael (emeritus) / Detmar, Michael (emeritus)
03816 - Halin Winter, Cornelia / Halin Winter, Cornelia
Funding
166490 - The role of lymphatic vessels in cancer progression (SNF)
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Show all metadata
Citations
Cited 35 times in
Web of Science
Cited 38 times in
Scopus
ETH Bibliography
yes
Altmetrics