Tille Jean-Christophe, Nisato Riccardo, Pepper Michael S
Department of Morphology, University Medical Center, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
Novartis Found Symp. 2004;256:112-31; discussion 132-6, 259-69.
The lymphatic system serves to collect and transport interstitial fluid (lymph) within tissues, and plays an important role in the immune response. The lymphatic system also constitutes one of most important pathways of tumour dissemination. In several human cancers, increased expression in primary tumours of a new member of the vascular endothelial growth factor (VEGF) family, namely VEGF-C, is correlated with regional lymph node metastasis. Experimental studies using transgenic mice overexpressing VEGF-C or xenotransplantation of VEGF-C-expressing tumour cells into immunodeficient mice have demonstrated a role for VEGF-C in tumour lymphangiogenesis and the subsequent formation of lymph node metastasis. However, there is at present very little evidence for lymphangiogenesis in human tumours, which is at variance with the data obtained in animal models. Nonetheless, the striking correlation between levels of VEGF-C in primary tumours and lymph node metastases exists. This suggests that VEGF-C may activate pre-existing lymphatics which then become actively involved in tumour cell chemotaxis, intralymphatic intravasation and distal dissemination. The role of VEGF-C in human tumour metastasis is therefore likely to involve lymphangiogenesis as well as its capacity to induce activation of pre-existing lymphatic endothelium.
淋巴系统负责收集和运输组织内的间质液（淋巴液），并在免疫反应中发挥重要作用。淋巴系统也是肿瘤扩散的最重要途径之一。在几种人类癌症中，血管内皮生长因子（VEGF）家族的一个新成员即VEGF-C在原发性肿瘤中的表达增加与区域淋巴结转移相关。使用过表达VEGF-C的转基因小鼠或将表达VEGF-C的肿瘤细胞异种移植到免疫缺陷小鼠中的实验研究已经证明VEGF-C在肿瘤淋巴管生成以及随后的淋巴结转移形成中起作用。然而，目前在人类肿瘤中淋巴管生成的证据非常少，这与在动物模型中获得的数据不一致。尽管如此，原发性肿瘤中VEGF-C水平与淋巴结转移之间存在显著相关性。这表明VEGF-C可能激活预先存在的淋巴管，然后这些淋巴管积极参与肿瘤细胞的趋化作用、淋巴管内血管侵入和远处扩散。因此，VEGF-C在人类肿瘤转移中的作用可能涉及淋巴管生成及其诱导预先存在的淋巴管内皮细胞激活的能力。
