Premium
Alteration of angiogenesis in H elicobacter heilmannii ‐induced mucosa‐associated lymphoid tissue lymphoma: Interaction with c‐ M et and hepatocyte growth factor
Author(s) -
Nakamura Masahiko,
Takahashi Tetsufumi,
Matsui Hidenori,
Baniwa Yuko,
Takahashi Shinichi,
Murayama Somay Y,
Serizawa Hiroshi,
Suzuki Hidekazu,
Hibi Toshifumi
Publication year - 2014
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/jgh.12776
Subject(s) - hepatocyte growth factor , lymphoma , malt lymphoma , bcl10 , lymphatic system , medicine , antibody , mucosa associated lymphoid tissue , pathology , cancer research , immunohistochemistry , angiogenesis , c met , immunology , receptor
Background and Aim The hepatocyte growth factor ( HGF )/c‐ M et 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‐ M et 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 H elicobacter heilmannii infection with c‐ M et and HGF . Methods C 57 BL /6 female mice, infected with H . heilmannii for 3 months were used. The localization of the HGF , c‐ M et, and HGF activator immunoreactivities was observed by the indirect immunohistochemical methods. In addition, the effect of c‐ M et antibody and c‐ M et inhibitor, PHA ‐665752, was also investigated. Results c‐ M et 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‐ M et or the c‐ M et 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‐ M et antibody or the c‐Met antagonist. Conclusions HGF and c‐ M et pathway were suggested to contribute to the lymphomagenesis in the MALT lymphoma after H . heilmannii infection.