Alteration of angiogenesis in Helicobacter heilmannii-induced mucosa-associated lymphoid tissue lymphoma: Interaction with c-Met and hepatocyte growth factor

Masahiko Nakamura, Tetsufumi Takahashi, Hidenori Matsui, Yuko Baniwa, Shinichi Takahashi, Somay Y. Murayama, Hiroshi Serizawa, Hidekazu Suzuki, Toshifumi Hibi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background and Aim: The hepatocyte growth factor (HGF)/c-Met pathway has attracted attention in the formation of malignant tumors, as HGF secreted from the microcirculatory components as well as residing macrophages has been suggested to act on the c-Met receptors of cancer cells to decrease apoptosis and increase proliferation, invasion, and metastasis. The present study was undertaken to elucidate the interaction of the gastric, hepatic, and pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma induced by Helicobacter heilmannii infection with c-Met and HGF. Methods: C57BL/6 female mice, infected with H.heilmannii for 3 months were used. The localization of the HGF, c-Met, and HGF activator immunoreactivities was observed by the indirect immunohistochemical methods. In addition, the effect of c-Met antibody and c-Met inhibitor, PHA-665752, was also investigated. Results: c-Met immunoreactivity was found in the lymphocytes composing the MALT lymphoma, and HGF immunoreactivity was recognized mostly in the endothelial cells and macrophages in the MALT lymphoma. HGFA was localized on mesenchymal cells other than the lymphocytes. The administration of the antibody against c-Met or the c-Met inhibitor to the infected mice induced the significant suppression of hepatic and pulmonary MALT lymphoma, while the gastric MALT lymphoma showed only a tendency to decrease in size, while the active caspase 3 positive cells markedly decreased in the gastric, hepatic, and pulmonary MALT lymphoma after the treatment with the c-Met antibody or the c-Met antagonist. Conclusions: HGF and c-Met pathway were suggested to contribute to the lymphomagenesis in the MALT lymphoma after H.heilmannii infection.

Original languageEnglish
Pages (from-to)70-76
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume29
Issue numberS4
DOIs
Publication statusPublished - 2014 Dec 1

Keywords

  • Angiogenesis
  • C-Met
  • HGF
  • MALT lymphoma

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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