Background and aims: Although it has been reported that intestinal metaplasia implicated in gastric carcinogenesis is induced by the ParaHox gene CDX2, it is unclear which genes are responsible for the formation of pseudopyloric glands and whether they play a role in gastric carcinogenesis. Pancreaticduodenal homeobox 1 (PDX1) is also a ParaHox gene which contributes to the genesis and development of the pancreas, duodenum, and antrum. To clarify its significance for the formation of pseudopyloric glands and gastric carcinogenesis, we investigated expression of PDX1 and mucin in gastric carcinomas and surrounding mucosa. Methods: Gastric carcinoma tissues from 95 patients were used for immunohistochemical analyses of PDX1, and mucins MUC6 and MUC5AC. Results: PDX1 was found to be frequently expressed in pseudopyloric glands and intestinal metaplasia. MUC6 was more abundant than MUC5AC in pseudopyloric glands while higher levels of MUC5AC than MUC6 were evident in intestinal metaplasia. The frequency of PDX1 positive reactivity was higher in differentiated type carcinomas (39/43, 90.7%) and T1 carcinomas (42/43, 97.7%) than in undifferentiated type (33/52, 63.5%) and T2-4 (30/52, 57.7%) carcinomas. PDX1 and MUC6 double positive expression was observed in carcinomas, respectively, including the corpus, and also correlated with histological type and depth of invasion. In contrast, no link was apparent between PDX1 and MUC5AC double positive reactivity and histological type. Conclusion: Our study suggests that PDX1 plays an important role in the development of pseudopyloric glands, and that pseudopyloric glands may reflect a condition associated with gastric carcinogenesis.

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Although glioblastoma (GBM) stem-like cells (GSCs), which retain chemo-radio resistance and recurrence, are key prognostic factors in GBM patients, the molecular mechanisms of GSC development are largely unknown. Recently, several studies revealed that extrinsic ribosome incorporation into somatic cells resulted in stem cell properties and served as a key trigger and factor for the cell reprogramming process. In this study, we aimed to investigate the mechanisms underlying GSCs development by focusing on extrinsic ribosome incorporation into GBM cells. Ribosome-induced cancer cell spheroid (RICCS) formation was significantly upregulated by ribosome incorporation. RICCS showed the stem-like cell characters (number of cell spheroid, stem cell markers, and ability for trans differentiation towards adipocytes and osteocytes). In RICCS, the phosphorylation and protein expression of ribosomal protein S6 (RPS6), an intrinsic ribosomal protein, and STAT3 phosphorylation were upregulated, and involved in the regulation of cell spheroid formation. Consistent with those results, glioma-derived extrinsic ribosome also promoted GBM-RICCS formation through intrinsic RPS6 phosphorylation. Moreover, in glioma patients, RPS6 phosphorylation was dominantly observed in high-grade glioma tissues, and predominantly upregulated in GSCs niches, such as the perinecrosis niche and perivascular niche. Those results indicate the potential biological and clinical significance of extrinsic ribosomal proteins in GSC development.