Yuuri Hatsuzawa1, Kazunori Yamaguchi2, Tomoka Takanashi3, Ikuro Sato4, Keiichi Tamai5, Mai Mochizuki5, Wataru Iwai6, Yuta Wakui6, Makoto Abue6, Kuniharu Yamamoto7, Jun Yasuda3, Masamichi Mizuma8, Michiaki Unno8, Kazuo Sugamura3. 1. Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, 9811293, Japan; Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, 9808575, Japan. 2. Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, 9811293, Japan; Department of Cancer Science, Tohoku University Graduate School of Medicine, Sendai, 9808575, Japan. Electronic address: kyamaguchi@med.tohoku.ac.jp. 3. Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, 9811293, Japan. 4. Department of Cancer Science, Tohoku University Graduate School of Medicine, Sendai, 9808575, Japan; Division of Pathology, Miyagi Cancer Center, Natori, 9811293, Japan. 5. Department of Cancer Science, Tohoku University Graduate School of Medicine, Sendai, 9808575, Japan; Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, 9811293, Japan. 6. Department of Gastroenterology, Miyagi Cancer Center, Natori, 9811293, Japan. 7. Department of Surgery, Tohoku Medical and Pharmaceutical University, Sendai, 9838536, Japan. 8. Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, 9808575, Japan.
Abstract
BACKGROUND: Accumulating evidence indicates that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is highly expressed in human epithelial carcinomas of multiple organs including the pancreas, but its functional role in carcinoma development has not yet been fully clarified. The aim of this study was to investigate the role of CD109 in the malignancy of pancreatic ductal adenocarcinoma (PDAC). METHODS: PDAC specimens of 145 cases were immunostained for CD109, and correlations between CD109 expression and clinicopathological conditions were analyzed. CD109 expression in PANC-1 cells, a PDAC-derived cell line, was decreased by siRNA or shRNA and its effect on the malignancy of PANC-1 cells was examined. RESULTS: Suppression of CD109 expression in PANC-1 cells resulted in reduction of in vitro cell motility and tumorigenicity in xenografts. Based on these results, we investigated the relationship between CD109 expression and metastasis of PDAC using tumor tissue specimens. Among 106 recurrent cases of 145 PDAC, there was a tendency for CD109-positive cases to be accompanied by distant metastasis. CONCLUSIONS: CD109 plays a critical role in the promotion of tumorigenic ability and cellular motility relating to metastasis of PDAC cells.
BACKGROUND: Accumulating evidence indicates that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is highly expressed in humanepithelial carcinomas of multiple organs including the pancreas, but its functional role in carcinoma development has not yet been fully clarified. The aim of this study was to investigate the role of CD109 in the malignancy of pancreatic ductal adenocarcinoma (PDAC). METHODS:PDAC specimens of 145 cases were immunostained for CD109, and correlations between CD109 expression and clinicopathological conditions were analyzed. CD109 expression in PANC-1 cells, a PDAC-derived cell line, was decreased by siRNA or shRNA and its effect on the malignancy of PANC-1 cells was examined. RESULTS: Suppression of CD109 expression in PANC-1 cells resulted in reduction of in vitro cell motility and tumorigenicity in xenografts. Based on these results, we investigated the relationship between CD109 expression and metastasis of PDAC using tumor tissue specimens. Among 106 recurrent cases of 145 PDAC, there was a tendency for CD109-positive cases to be accompanied by distant metastasis. CONCLUSIONS:CD109 plays a critical role in the promotion of tumorigenic ability and cellular motility relating to metastasis of PDAC cells.