Suppression of lymphangiogenesis induced by Flt-4 antibody in gastric low-grade mucosa-associated lymphoid tissue lymphoma by Helicobacter heilmannii infection
Suppression of lymphangiogenesis induced by Flt-4 antibody in gastric low-grade mucosa-associated lymphoid tissue lymphoma by Helicobacter heilmannii infection
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DOI：
10.1111/j.1440-1746.2010.06230.x
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发表时间：
2010-05-01
影响因子：
4.1
通讯作者：
Tsuchimoto, Kanji
中科院分区：
文献类型：
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作者：
Nakamura, Masahiko;Matsui, Hidenori;Tsuchimoto, Kanji
背景和目的：我们最近的研究显示，C57BL/6小鼠经口腔感染后6个月可在胃底诱发低级别黏膜相关淋巴组织（MALT）淋巴瘤，但淋巴瘤扩张的病理生理机制尚不清楚。本研究旨在阐明该肿瘤与血管生成和淋巴管生成的相互作用。此外，我们还研究了Flt-4抗体对淋巴瘤扩展的影响。方法：以感染海曼螺杆菌3个月的C57BL/6雌性小鼠为实验对象。采用间接免疫组织化学方法检测血管内皮生长因子C （VEGF-C）和Flt-4的免疫反应性。通过prox-1的定位研究淋巴和血管内皮细胞的定位。此外，将Flt-4抗体（含Flt-1抗体和不含Flt-1抗体）或Flk-1抗体口服，以明确其对肿瘤大小的影响。结果：MALT淋巴瘤具有丰富的微血管网络，由未成熟的毛细血管、淋巴管和小静脉组成。免疫组化分析显示，prox-1免疫反应主要出现在淋巴瘤边缘区域，VEGF-C和Flt-4免疫反应也出现在边缘区域。体视显微镜研究显示，给药Flt-4和Flt-1抗体可显著减少小鼠胃淋巴瘤的表面积。结论：VEGF- c介导的机制在MALT淋巴瘤的扩张中起重要作用，VEGF受体抗体对肿瘤生长有抑制作用。
Background and Aims:Our recent study revealed that per oral infection with Helicobacter heilmannii induced low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the gastric fundus of C57BL/6 mice after a period of 6 months, although the pathophysiological mechanism of lymphoma expansion remains to be clarified. The present study was undertaken to elucidate the interaction of this tumor with angiogenesis and lymphangiogenesis. In addition, the effect of Flt-4 antibodies on lymphoma expansion was investigated.Methods:C57BL/6 female mice infected with H. heilmannii for 3 months were used in the experiments. Localization of vascular endothelial growth factor C (VEGF-C) and Flt-4 immunoreactivity were detected by indirect immunohistochemical methods. Localization of lymphatic and vascular endothelial cells was investigated by localization of prox-1. In addition, Flt-4 antibody with and without Flt-1 or Flk-1 antibodies was administered i.p. to clarify their effects on tumor size.Results:MALT lymphoma has a rich microvascular network consisting of immature capillaries, lymphatics and venules. By immunohistochemical analysis, prox-1 immunoreactivity was observed mostly in the marginal area of the lymphoma, where VEGF-C and Flt-4 immunoreactivities were also seen. Stereomicroscopic study revealed that administration of Flt-4 and Flt-1 antibodies significantly reduced the surface area of the lymphoma in the mouse stomach.Conclusion:A VEGF-C-mediated mechanism plays an important role in the expansion of MALT lymphoma and the administration of VEGF receptor antibodies had a suppressive effect on tumor growth.