Distinct Localization of Mature HGF from its Precursor Form in Developing and Repairing the Stomach

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain HGF (scHGF); however, only proteolytically processed two-chain HGF (tcHGF) can activate the MET receptor. We investigated the localization of tcHGF and activated/phosphorylated MET (pMET) using a tcHGF-specific antibody. In day 16.5 mouse embryos, total HGF (scHGF + tcHGF) was mainly localized in smooth muscle cells close to, but separate from, MET-positive epithelial cells in endodermal organs, including the stomach. In the adult stomach, total HGF was localized in smooth muscle cells, and tcHGF was mainly localized in the glandular base region. Immunostaining for pMET and Lgr5-driven green fluorescent protein (GFP) indicated that pMET localization overlapped with Lgr5+ gastric stem cells. HGF promoted organoid formation similar to EGF, indicating the potential for HGF to promote the survival and growth of gastric stem cells. pMET and tcHGF localizations changed during regeneration following gastric injury. These results indicate that MET is constantly activated in gastric stem cells and that the localization of pMET differs from the primary localization of precursor HGF but has a close relationship to tcHGF. Our results suggest the importance of the microenvironmental generation of tcHGF in the regulation of development, regeneration, and stem cell behavior.

Expression of Angiogenin is inversely correlated to Progression of Gastric Tumors

Objective: Angiogenin (ANG) is upregulated in a variety of cancers including those of prostate, cervix, pancreas, liver, oral cavity, skin, and etc., however, the role of ANG in gastric cancer has not been fully elucidated yet. We use tissue microarray (TMA) to examine ANG expression to investigate the role of ANG in the progression of gastric cancer. Method: Immunohistochemistry was used to evaluate ANG expression in TMA with 208 spots from 104 patients diagnosed with gastric cancer and the corresponding adjacent tissue. Results: In normal adjacent tissue, ANG was expressed mainly in cytoplasm at basal gland of the gastric mucus where gastric stem cells are reserved, and also sparsely expressed in the nucleus of gastric mucosal gland cells at isthmus where gastric stem cells are gathered. In cancer tissues, ANG was very sparsely expressed in the nucleus of gastric glandular cells. ANG expression in the cytoplasm was found to be significantly associated with pathological types (p<0.001) and malignancy (p<0.001). ANG expression in the nucleus was inversely correlated with malignancy (p=0.019), differentiation status (p< 0.001), and tumor stage (p= 0.048).Conclusion: ANG might play an important role in gastric cancer development.