MALT Lymphoma Stem Cell and its Niche in Helicobacter heilmannii‐infected Mice Stomach

Abstract

Background & AimsAlthough cancer and leukemia stem cells are indispensable in the initiation and enlargement of lesions, the gastric MALT lymphoma is thought to be polyclonal with the persistent infection of Helicobacter species and then change to monoclonal with genetic aberrations, and the participation of stem cells in the tumor formation remains to be elucidated. We performed a histochemical analysis in Helicobacter heilmannii‐induced gastric and hepatic MALT lymphoma in the infected alone and eradicated after infection groups.Materials and MethodsWe used a Helicobacter heilmannii sample isolated from the stomach of a cynomolgus monkey and maintained in C57BL/6 mouse stomachs. Mucosal homogenates were used to inoculate C57BL/6 mice, which were then examined over 24 months. Macroscopic observations were carried out, and PCR analysis of the bacteria of the Helicobacter species was performed at intervals over the observation period. Histochemical analysis was performed using the gastric and hepatic MALT lymphoma with monoclonal and polyclonal stem cell‐related antibodies against doublecortin‐like kinase (DCAMKL1), Musashi‐1, proliferating cell nuclear antigen (PCNA), CD44, CD133, as well as myofibroblast, endothelial, and pericyte markers.ResultsDCAMKL1, Musashi‐1, CD144 positivities were not recognized in the early stage of the lymphoma formation but gradually found in the lymphocytes located in the marginal zone of the MALT lymphoma both in the gastric and hepatic MALT lymphoma. The well‐developed microcirculatory network accompanied the stem cell rich area. The myofibroblasts were also distributed in these area, suggesting the formation of stem cell niche similar to that found in epithelial cells.ConclusionsMALT lymphoma stem cells were found to exist in the marginal zone of the lymphoma, constituting the niche by the myofibroblast and microcirculatory components.