heilmannii for 3 months were used. The localization selleck inhibitor 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. 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. OSI-906 cell line HGF and c-Met pathway were suggested to contribute to the lymphomagenesis in the MALT lymphoma after H. heilmannii infection. Our recent study has revealed that the oral infection of Helicobacter heilmannii obtained from cynomolgus monkeys induced the gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in almost all C57BL/6 mice after a period of 6 months.[1] The eradication treatment by the triple therapy applied for H. pylori, that is, combination of two kinds of antibiotics and a proton

pump inhibitor, has failed to eliminate the H. heilmannii.[2] Thus, a new therapy other Nintedanib (BIBF 1120) than the eradication of the bacteria requires to be invented. The hepatocyte growth factor (HGF)/c-Met pathway and vascular endothelial growth factor (VEGF)/VEGF receptor pathway have attracted attention as key players in the proliferation, invasion, and metastasis of malignant tumors. Here, we focus on the role of the HGF and its receptor, c-Met, during the formation and progression of the gastric, hepatic, and pulmonary low-grade MALT type B-cell lymphoma from the viewpoint of angiogenesis. We identified urease-positive bacteria infecting the stomach of cynomolgus monkeys in 1994.[3] We then used the gastric mucosal and mucus homogenates for inoculation of C3H/HeJ mice by per oral administration, and the infected mice were maintained under standard laboratory conditions for periods ranging from 3 to 24 months. In 6-month intervals (20 times, total: 120 months), we inoculated naïve C3H/HeJ mice using gastric mucosal and mucus homogenates from infected mice to maintain the isolate. In the present experiment, 6-week-old C57BL/6 mice were inoculated with gastric mucosal homogenates containing gastric mucus and mucosa from infected C3H/HeJ mice 3 months prior to the experiment. The H. heilmannii-infected mice were divided into the following three groups: phosphate-buffered saline-treated group, c-Met antibody-treated group, and PHA-665752-treated group.