Department of Vascular Biology, Institute of Development, Tohoku University, Aoba-ku, Sendai 980-8575, Japan.
Am J Pathol. 2010 Apr;176(4):1950-8. doi: 10.2353/ajpath.2010.090829. Epub 2010 Feb 4.
During cancer progression, the angiogenesis that occurs is involved in tumor growth and hematogenous-distant metastasis, whereas lymphangiogenesis is involved in regional lymph node metastasis. Angiogenesis is counterregulated by various endogenous inhibitors; however, little is known about endogenous inhibitors of lymphangiogenesis. We recently isolated vasohibin1 as an angiogenesis inhibitor intrinsic to the endothelium and further demonstrated its anticancer activity through angiogenesis inhibition. Here, we examined the effect of vasohibin1 on lymphangiogenesis. Vasohibin1 exhibited broad-spectrum antilymphangiogenic activity in the mouse cornea induced by factors including VEGF-A, VEGF-C, FGF2, and PDGF-BB. We then inoculated highly lymph node-metastatic cancer cells into mice and examined the effect of vasohibin1 on lymph node metastasis. Tail-vein injection of adenovirus containing the human vasohibin1 gene inhibited tumor lymphangiogenesis and regional lymph node metastasis. Moreover, local injection of recombinant vasohibin1 inhibited lymph node metastasis. These results suggest vasohibin1 to be the first known intrinsic factor having broad-spectrum antilymphangiogenic activity and indicate that it suppresses lymph node metastasis.
在癌症进展过程中，发生的血管生成参与肿瘤生长和血行远处转移，而淋巴管生成则参与区域淋巴结转移。血管生成受到各种内源性抑制剂的调节；然而，关于淋巴管生成的内源性抑制剂知之甚少。我们最近分离出血管抑素 1 作为内皮固有血管生成抑制剂，并通过抑制血管生成进一步证明其抗癌活性。在这里，我们检查了血管抑素 1 对淋巴管生成的影响。血管抑素 1 在由 VEGF-A、VEGF-C、FGF2 和 PDGF-BB 等因子诱导的小鼠角膜中表现出广谱抗淋巴管生成活性。然后，我们将高度淋巴结转移性癌细胞接种到小鼠中，并检查血管抑素 1 对淋巴结转移的影响。静脉内注射含有人血管抑素 1 基因的腺病毒抑制肿瘤淋巴管生成和区域淋巴结转移。此外，重组血管抑素 1 的局部注射抑制了淋巴结转移。这些结果表明血管抑素 1 是第一个具有广谱抗淋巴管生成活性的已知固有因子，并表明它抑制了淋巴结转移。
