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Int. J. Mol. Sci. 2017, 18(1), 51; doi:10.3390/ijms18010051

Lymph Nodes and Cancer Metastasis: New Perspectives on the Role of Intranodal Lymphatic Sinuses

Faculty of Welfare and Health Science, Oita University, Oita 870-1192, Japan
Academic Editor: Li Yang
Received: 25 October 2016 / Revised: 21 December 2016 / Accepted: 23 December 2016 / Published: 28 December 2016
(This article belongs to the Special Issue Tumor Microenvironment and Metabolism)
View Full-Text   |   Download PDF [3039 KB, uploaded 28 December 2016]   |  

Abstract

The lymphatic system is essential for transporting interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs). Functional integrity of LNs is dependent on intact lymphatics and effective lymph drainage. Molecular mechanisms that facilitate interactions between tumor cells and lymphatic endothelial cells (LECs) during tumor progression still remain to be identified. The cellular and molecular structures of LNs are optimized to trigger a rapid and efficient immune response, and to participate in the process of tumor metastasis by stimulating lymphangiogenesis and establishing a premetastatic niche in LNs. Several molecules, e.g., S1P, CCR7-CCL19/CCL21, CXCL12/CXCR4, IL-7, IFN-γ, TGF-β, and integrin α4β1 play an important role in controlling the activity of LN stromal cells including LECs, fibroblastic reticular cells (FRCs) and follicular dendritic cells (DCs). The functional stromal cells are critical for reconstruction and remodeling of the LN that creates a unique microenvironment of tumor cells and LECs for cancer metastasis. LN metastasis is a major determinant for the prognosis of most human cancers and clinical management. Ongoing work to elucidate the function and molecular regulation of LN lymphatic sinuses will provide insight into cancer development mechanisms and improve therapeutic approaches for human malignancy. View Full-Text
Keywords: lymph nodes; lymphatic endothelial cells; cancer metastasis; lymphangiogenesis; VEGF-A/-C/-D lymph nodes; lymphatic endothelial cells; cancer metastasis; lymphangiogenesis; VEGF-A/-C/-D
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Ji, R.-C. Lymph Nodes and Cancer Metastasis: New Perspectives on the Role of Intranodal Lymphatic Sinuses. Int. J. Mol. Sci. 2017, 18, 51.

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