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Suppression of lymphangiogenesis induced by Flt‐4 antibody in gastric low‐grade mucosa‐associated lymphoid tissue lymphoma by Helicobacter heilmannii infection
Author(s) -
Nakamura Masahiko,
Matsui Hidenori,
Takahashi Tetsufumi,
Ogawa Satoshi,
Tamura Ryo,
Murayama Somay Y,
Takahashi Shinichi,
Tsuchimoto Kanji
Publication year - 2010
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2010.06230.x
Subject(s) - lymphangiogenesis , lymphatic system , lymphoma , pathology , medicine , immunohistochemistry , malt lymphoma , angiogenesis , antibody , cancer , cancer research , immunology , metastasis
Abstract 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.