Chronic inflammation with Helicobacter pylori infection is implicated in CD44 overexpression through miR-328 suppression in the gastric mucosa
Tóm tắt
Infection with Helicobacter pylori is the main risk factor for development of gastric cancer. CD44 overexpression, especially that of variant 9 (CD44v9), has also been implicated in the local inflammatory response and metaplasia–carcinoma sequence in human stomach. We recently identified miR-328 as one of the microRNAs targeting CD44 in gastric cancer. The aim of the current study was to determine the relationship between miR-328 and CD44v9 expression in H. pylori-infected gastric mucosa during the development of preneoplastic lesions. Immunohistochemical staining of myeloperoxidase and CD44v9 was performed using paraffin-embedded tissue sections obtained from 54 patients who underwent gastric resection without preoperative treatment. The levels of miR-328 expression in the gastric mucosa were measured in the same patients using quantitative reverse transcription polymerase chain reaction. Both infiltration of myeloperoxidase-positive inflammatory cells and expression of proinflammatory cytokines closely correlated with H. pylori infection in the cancer-afflicted gastric mucosa. High CD44v9 expression levels, identified in the gastric mucosa in 61 % of samples (33/54), correlated significantly with H. pylori infection in the gastric mucosa. Notably, high CD44v9 expression was significantly associated with low miR-328 expression, whereas low CD44v9 expression was significantly associated with high miR-328 expression. We showed that miR-328 downregulation and de novo expression of CD44v9 occurred in H. pylori-infected gastric mucosa adjacent to gastric cancer compared with gastric mucosa not infected with H. pylori adjacent to gastric cancer. CD44v9-overexpressing cells are known to acquire reactive oxygen species resistance; thus, these cells may avoid cell death caused by various stress inducers, which may be linked to the origin of gastric cancer development.
Tài liệu tham khảo
Hohenberger P, Gretschel S. Gastric cancer. Lancet. 2003;362(9380):305–15.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.
Peek RM Jr, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2(1):28–37.
Nomura S, Baxter T, Yamaguchi H, Leys C, Vartapetian AB, Fox JG, et al. Spasmolytic polypeptide expressing metaplasia to preneoplasia in H. felis-infected mice. Gastroenterology. 2004;127(2):582–94.
Nozaki K, Ogawa M, Williams JA, Lafleur BJ, Ng V, Drapkin RI, et al. A molecular signature of gastric metaplasia arising in response to acute parietal cell loss. Gastroenterology. 2008;134(2):511–22.
Schmidt PH, Lee JR, Joshi V, Playford RJ, Poulsom R, Wright NA, et al. Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Investig 1999;79(6):639–46.
Yamaguchi H, Goldenring JR, Kaminishi M, Lee JR. Identification of spasmolytic polypeptide expressing metaplasia (SPEM) in remnant gastric cancer and surveillance postgastrectomy biopsies. Dig Dis Sci. 2002;47(3):573–8.
Halldorsdottir AM, Sigurdardottrir M, Jonasson JG, Oddsdottir M, Magnusson J, Lee JR, et al. Spasmolytic polypeptide-expressing metaplasia (SPEM) associated with gastric cancer in Iceland. Dig Dis Sci. 2003;48(3):431–41.
Oshima H, Oshima M, Inaba K, Taketo MM. Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice. EMBO J. 2004;23(7):1669–78.
Oshima H, Matsunaga A, Fujimura T, Tsukamoto T, Taketo MM, Oshima M. Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology. 2006;131(4):1086–95.
Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev. 2003;4(1):33–45.
Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc− and thereby promotes tumor growth. Cancer Cell. 2011;19(3):387–400.
Nagano O, Okazaki S, Saya H. Redox regulation in stem-like cancer cells by CD44 variant isoforms. Oncogene. 2013;32(44):5191–8.
Fan X, Long A, Goggins M, Fan X, Keeling PW, Kelleher D. Expression of CD44 and its variants on gastric epithelial cells of patients with Helicobacter pylori colonisation. Gut. 1996;38(4):507–12.
Wada T, Ishimoto T, Seishima R, Tsuchihashi K, Yoshikawa M, Oshima H, et al. Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia. Cancer Sci. 2013;104(10):1323–9.
Ishimoto T, Sugihara H, Watanabe M, Sawayama H, Iwatsuki M, Baba Y, et al. Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in cancer cells and promote redox adaptation. Carcinogenesis. 2014;35(5):1003–11.
Higashikawa K, Yokozaki H, Ue T, Taniyama K, Ishikawa T, Tarin D, et al. Evaluation of CD44 transcription variants in human digestive tract carcinomas and normal tissues. Int J Cancer. 1996;66(1):11–7.
Dhingra S, Feng W, Brown RE, Zhou Z, Khoury T, Zhang R, et al. Clinicopathologic significance of putative stem cell markers, CD44 and nestin, in gastric adenocarcinoma. Int J Clin Exp Pathol. 2011;4(8):733–41.
Khurana SS, Riehl TE, Moore BD, Fassan M, Rugge M, Romero-Gallo J, et al. The hyaluronic acid receptor CD44 coordinates normal and metaplastic gastric epithelial progenitor cell proliferation. J Biol Chem. 2013;288(22):16085–97.
Zeilstra J, Joosten SP, Dokter M, Verwiel E, Spaargaren M, Pals ST. Deletion of the WNT target and cancer stem cell marker CD44 in Apc(Min/+) mice attenuates intestinal tumorigenesis. Cancer Res. 2008;68(10):3655–61.
Ishimoto T, Oshima H, Oshima M, Kai K, Torii R, Masuko T, et al. CD44+ slow-cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis. Cancer Sci. 2010;101(3):673–8.
Gee K, Lim W, Ma W, Nandan D, Diaz-Mitoma F, Kozlowski M, et al. Differential regulation of CD44 expression by lipopolysaccharide (LPS) and TNF-α in human monocytic cells: distinct involvement of c-Jun N-terminal kinase in LPS-induced CD44 expression. J Immunol. 2002;169(10):5660–72.
Muthukumaran N, Miletti-Gonzalez KE, Ravindranath AK, Rodriguez-Rodriguez L. Tumor necrosis factor-α differentially modulates CD44 expression in ovarian cancer cells. Mol Cancer Res. 2006;4(8):511–20.
Takahashi E, Nagano O, Ishimoto T, Yae T, Suzuki Y, Shinoda T, et al. Tumor necrosis factor-α regulates transforming growth factor-β-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction. J Biol Chem. 2010;285(6):4060–73.
Krishnamachary B, Penet MF, Nimmagadda S, Mironchik Y, Raman V, Solaiyappan M, et al. Hypoxia regulates CD44 and its variant isoforms through HIF-1α in triple negative breast cancer. PLoS One. 2012;7(8):e44078.
Nishizawa T, Suzuki H. The role of microRNA in gastric malignancy. Int J Mol Sci. 2013;14(5):9487–96.
Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011;17(2):211–5.
Cheng W, Liu T, Wan X, Gao Y, Wang H. MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J. 2012;279(11):2047–59.
Tovuu LO, Imura S, Utsunomiya T, Morine Y, Ikemoto T, Arakawa Y, et al. Role of CD44 expression in non-tumor tissue on intrahepatic recurrence of hepatocellular carcinoma. Int J Clin Oncol. 2013;18(4):651–6.
Utsunomiya T, Ishikawa D, Asanoma M, Yamada S, Iwahashi S, Kanamoto M, et al. Specific miRNA expression profiles of non-tumor liver tissue predict a risk for recurrence of hepatocellular carcinoma. Hepatol Res. 2014;44(6):631–8.