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

被引:55
作者
Commerford, Catharina D. [1 ]
Dieterich, Lothar C. [1 ]
He, Yuliang [1 ]
Hell, Tanja [1 ]
Montoya-Zegarra, Javier A. [1 ,2 ]
Noerrelykke, Simon F. [2 ]
Russo, Erica [1 ]
Roecken, Martin [3 ]
Detmar, Michael [1 ]
机构
[1] Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland
[2] Swiss Fed Inst Technol, Sci Ctr Opt & Electron Microscopy, CH-8093 Zurich, Switzerland
[3] Eberhard Karls Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany
来源
CELL REPORTS | 2018年 / 25卷 / 13期
基金
瑞士国家科学基金会; 欧洲研究理事会;
关键词
ENDOTHELIAL GROWTH-FACTOR; BLOOD-VESSELS; LYMPHANGIOGENESIS; METASTASIS; PROMOTES; INVOLVEMENT; FIBRINOGEN; CELLS; DISSEMINATION; ANGIOGENESIS;
D O I
10.1016/j.celrep.2018.12.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 alpha IIb 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 aIIb 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.
引用
收藏
页码:3554 / +
页数:14
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