Annexin A10 is involved in the induction of pancreatic duodenal homeobox‑1 in gastric cancer tissue, cells and organoids

Ishikawa,Akira; Sakamoto,Naoya; Honma,Ririno; Taniyama,Daiki; Fukada,Kaho; Hattori,Takuya; Sentani,Kazuhiro; Oue,Naohide; Yanagihara,Kazuyoshi; Tanabe,Kazuaki; Ohdan,Hideki; Yasui,Wataru

doi:10.3892/or.2019.7422

Annexin A10 is involved in the induction of pancreatic duodenal homeobox‑1 in gastric cancer tissue, cells and organoids

Authors:
- Akira Ishikawa
- Naoya Sakamoto
- Ririno Honma
- Daiki Taniyama
- Kaho Fukada
- Takuya Hattori
- Kazuhiro Sentani
- Naohide Oue
- Kazuyoshi Yanagihara
- Kazuaki Tanabe
- Hideki Ohdan
- Wataru Yasui
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Affiliations: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734‑8551, Japan, Division of Biomarker Discovery, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo 277‑8577, Japan, Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734‑8551, Japan
Published online on: December 2, 2019 https://doi.org/10.3892/or.2019.7422
Pages: 581-590

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Abstract

Gastric cancer (GC) is the third most common cause of cancer‑related death in the world. Annexin A10 (ANXA10), a member of the Annexin family, is a calcium‑/phospholipid‑binding protein; however, little is known concerning its functions. It is still unclear what molecule is involved in the induction of ANXA10. In the present study, we performed immunohistochemistry to evaluate the expression of ANXA10, pancreatic and duodenal homeobox‑1 (PDX1) and mucin phenotype markers in 130 GC samples. ANXA10 was detected in 63 (48%) of the 130 GC cases and loss of ANXA10 was significantly correlated with disease progression and poor clinical outcomes in GC. PDX1 was significantly correlated with ANXA10 in GC cases and cell lines. Although PDX1 was not significantly correlated with the GC cases with any of the mucin phenotypes, ANXA10 was preferentially detected in the GC cases with the gastric mucin phenotype. As a further investigation, we generated organoids derived from human GC and identified the duplication of the mucin phenotypes of GC by immunohistochemistry. The repression effect on cell growth that was observed in the ANXA10‑knockdown cell lines was also clearly observed in the human gastric organoids. We demonstrated that the expression of ANXA10 was correlated with the gastric mucin phenotype and ANXA10 was involved in the induction of PDX1 expression in GC. We also provided evidence that GC organoids represent a powerful tool for scrutinizing the biology of GC, especially with regard to the mucin phenotype.

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1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
2	Oue N, Sentani K, Sakamoto N and Yasui W: Clinicopathologic and molecular characteristics of gastric cancer showing gastric and intestinal mucin phenotype. Cancer Sci. 106:951–958. 2015. View Article : Google Scholar : PubMed/NCBI
3	Lauren P: The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 64:31–49. 1965. View Article : Google Scholar : PubMed/NCBI
4	Endoh Y, Sakata K, Tamura G, Ohmura K, Ajioka Y, Watanabe H and Motoyama T: Cellular phenotypes of differentiated-type adenocarcinomas and precancerous lesions of the stomach are dependent on the genetic pathways. J Pathol. 191:257–263. 2000. View Article : Google Scholar : PubMed/NCBI
5	Ohnishi M, Tokuda M, Masaki T, Fujimura T, Tai Y, Matsui H, Itano T, Ishida T, Takahara J and Konishi R: Changes in annexin I and II levels during the postnatal development of rat pancreatic islets. J Cell Sci. 107:2117–2125. 1994.PubMed/NCBI
6	Gerke V and Moss SE: Annexins: From structure to function. Physiol Rev. 82:331–371. 2002. View Article : Google Scholar : PubMed/NCBI
7	Lu SH, Chen YL, Shun CT, Lai JN, Peng SY, Lai PL and Hsu HC: Expression and prognostic significance of gastric-specific annexin A10 in diffuse- and intestinal-type gastric carcinoma. J Gastroenterol Hepatol. 26:90–97. 2011. View Article : Google Scholar : PubMed/NCBI
8	Lu SH, Yuan RH, Chen YL, Hsu HC and Jeng YM: Annexin A10 is an immunohistochemical marker for adenocarcinoma of the upper gastrointestinal tract and pancreatobiliary system. Histopathology. 63:640–648. 2013.PubMed/NCBI
9	Kodaira H, Koma YI, Hosono M, Higashino N, Suemune K, Nishio M, Shigeoka M and Yokozaki H: ANAX10 induction by interaction with tumor-associated macrophages the growth of esophageal squamous cell carcinoma. Pathol Int. 69:135–147. 2019. View Article : Google Scholar : PubMed/NCBI
10	Shimizu T, Kasamatsu A, Yamamoto A, Koike K, Ishige S, Takatori H, Sakamoto Y, Ogawara K, Shiiba M, Tanzawa H and Uzawa K: Annexin A10 in human oral cancer: Biomarker for tumoral growth via G1/S transition by targeting MAPK signaling pathways. PLoS One. 7:e455102012. View Article : Google Scholar : PubMed/NCBI
11	Masaki T, Tokuda M, Ohnishi M, Watanabe S, Fujimura T, Miyamoto K, Itano T, Matsui H, Arima K, Shirai M, et al: Enhanced expression of the protein kinase substrate annexin in human hepatocellular carcinoma. Hepatology. 24:72–81. 1996. View Article : Google Scholar : PubMed/NCBI
12	Kim JH, Rhee YY, Kim KJ, Cho NY, Lee HS and Kang GH: Annexin A10 expression correlates with serrated pathway features in colorectal carcinoma with microsatellite instability. APMIS. 122:1187–1195. 2014. View Article : Google Scholar : PubMed/NCBI
13	Tsai JH, Lin YL, Cheng YC, Chen CC, Lin LI, Tseng LH, Cheng ML, Liau JY and Jeng YM: Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma. Mod Pathol. 28:268–278. 2015. View Article : Google Scholar : PubMed/NCBI
14	Gonzalo DH, Lai KK, Shadrach B, Goldblum JR, Bennett AE, Downs-Kelly E, Liu X, Henricks W, Patil DT, Carver P, et al: Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp. J Pathol. 230:420–429. 2013. View Article : Google Scholar : PubMed/NCBI
15	Bartley AN, Thompson PA, Buckmeier JA, Kepler CY, Hsu CH, Snyder MS, Lance P, Bhattacharyya A and Hamilton SR: Expression of gastric pyloric mucin, MUC6, in colorectal serrated polyps. Mod Pathol. 23:169–176. 2010. View Article : Google Scholar : PubMed/NCBI
16	Gibson JA, Hahn HP, Shahsafaei A and Odze RD: MUC expression in hyperplastic and serrated colonic polyps: Lack of specificity of MUC6. Am J Surg Pathol. 35:742–749. 2011. View Article : Google Scholar : PubMed/NCBI
17	Walsh MD, Clendenning M, Williamson E, Pearson SA, Walters RJ, Nagler B, Packenas D, Win AK, Hopper JL, Jenkins MA, et al: Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype. Mod Pathol. 26:1642–1656. 2013. View Article : Google Scholar : PubMed/NCBI
18	Kim J, Kim MA, Jee CD, Jung EJ and Kim WH: Reduced expression and homozygous deletion of annexin A10 in gastric carcinoma. Int J Cancer. 125:1842–1850. 2009. View Article : Google Scholar : PubMed/NCBI
19	Kim JK, Kim PJ, Jung KH, Noh JH, Eun JW, Bae HJ, Xie HJ, Shan JM, Ping WY, Park WS, et al: Decreased expression of Annexin A10 in gastric cancer and its overexpression in tumor cell growth suppression. Oncol Rep. 24:607–612. 2010.PubMed/NCBI
20	Brooke NM, Garcia-Fernàndez J and Holland PW: The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature. 392:920–922. 1998. View Article : Google Scholar : PubMed/NCBI
21	Koizumi M, Doi R, Toyoda E, Masui T, Tulachan SS, Kawaguchi Y, Fujimoto K, Gittes GK and Imamura M: Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer. Surgery. 134:260–266. 2003. View Article : Google Scholar : PubMed/NCBI
22	Ma J, Chen M, Wang J, Xia HH, Zhu S, Liang Y, Gu Q, Qiao L, Dai Y, Zou B, et al: Pancreatic duodenal homeobox-1 (PDX1) functions as a tumor suppressor in gastric cancer. Carcinogenesis. 29:1327–1333. 2008. View Article : Google Scholar : PubMed/NCBI
23	Sakamoto N, Feng Y, Stolfi C, Kurosu Y, Green M, Lin J, Green ME, Sentani K, Yasui W, McMahon M, et al: BRAFV600E cooperates with CDX2 inactivation to promote serrated colorectal tumorigenesis. Elife. 6:e203312017. View Article : Google Scholar : PubMed/NCBI
24	Yanagihara K, Tanaka H, Takigahira M, Ino Y, Yamaguchi Y, Toge T, Sugano K and Hirohashi S: Establishment of two cell lines from human gastric scirrhous carcinoma that possess the potential to metastasize spontaneously in nude mice. Cancer Sci. 95:575–582. 2004. View Article : Google Scholar : PubMed/NCBI
25	Yasui W, Ayhan A, Kitadai Y, Nishimura K, Yokozaki H, Ito H and Tahara E: Increased expression of p34cdc2 and its kinase activity in human gastric and colonic carcinomas. Int J Cancer. 53:36–41. 1993. View Article : Google Scholar : PubMed/NCBI
26	Sakamoto N, Naito Y, Oue N, Sentani K, Uraoka N, Oo HZ, Yanagihara K, Aoyagi K, Sasaki H and Yasui W: MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis. Cancer Sci. 105:236–243. 2014. View Article : Google Scholar : PubMed/NCBI
27	Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, Ichinose S, Nagaishi T, Okamoto R, Tsuchiya K, et al: Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5⁺ stem cell. Nat Med. 18:618–623. 2012. View Article : Google Scholar : PubMed/NCBI
28	Koo BK, Sasselli V and Clevers H: Retroviral gene expression control in primary organoid cultures. Curr Protoc Stem Cell Biol. 27:Unit 5A.6. 2013. View Article : Google Scholar : PubMed/NCBI
29	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
30	Kim TH and Shivdasani RA: Stomach development, stem cells and disease. Development. 143:554–565. 2016. View Article : Google Scholar : PubMed/NCBI
31	Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ and Clevers H: Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 459:262–265. 2009. View Article : Google Scholar : PubMed/NCBI
32	Fujii M, Shimokawa M, Date S, Takano A, Matano M, Nanki K, Ohta Y, Toshimitsu K, Nakazato Y, Kawasaki K, et al: A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell. 18:827–838. 2016. View Article : Google Scholar : PubMed/NCBI
33	Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, Vries R, Peters PJ and Clevers H: In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology. 148:126–136.e126. 2015. View Article : Google Scholar : PubMed/NCBI
34	Cancer Genome Atlas Research Network, . Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 513:202–209. 2014. View Article : Google Scholar : PubMed/NCBI
35	van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F, Pronk A, van Houdt W, van Gorp J, Taylor-Weiner A, Kester L, et al: Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 161:933–945. 2015. View Article : Google Scholar : PubMed/NCBI