Ji Rui-Cheng
Faculty of Welfare and Health Science, Oita University, Oita 870-1192, Japan.
Int J Mol Sci. 2016 Dec 28;18(1):51. doi: 10.3390/ijms18010051.
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.
淋巴系统对于将组织间液、可溶性抗原和免疫细胞从外周组织运输至淋巴结至关重要。淋巴结的功能完整性取决于完整的淋巴管和有效的淋巴引流。肿瘤进展过程中促进肿瘤细胞与淋巴管内皮细胞（LECs）相互作用的分子机制仍有待确定。淋巴结的细胞和分子结构经过优化，以触发快速有效的免疫反应，并通过刺激淋巴管生成和在淋巴结中建立前转移微环境参与肿瘤转移过程。几种分子，如鞘氨醇-1-磷酸（S1P）、趋化因子受体7-巨噬细胞炎性蛋白-3β/次级淋巴组织趋化因子（CCR7-CCL19/CCL21）、基质细胞衍生因子-1α/趋化因子受体4（CXCL12/CXCR4）、白细胞介素-7（IL-7）、干扰素-γ（IFN-γ）、转化生长因子-β（TGF-β）和整合素α4β1，在控制包括淋巴管内皮细胞、成纤维网状细胞（FRCs）和滤泡树突状细胞（DCs）在内的淋巴结基质细胞的活性方面发挥重要作用。功能性基质细胞对于淋巴结的重建和重塑至关重要，而淋巴结的重建和重塑为肿瘤细胞和淋巴管内皮细胞创造了独特的微环境以促进癌症转移。淋巴结转移是大多数人类癌症预后和临床管理的主要决定因素。阐明淋巴结淋巴窦功能和分子调控的正在进行的工作将为癌症发展机制提供见解，并改善人类恶性肿瘤的治疗方法。
