Establishment and biological characterization of a novel cell line derived from hepatoid adenocarcinoma originated at the ampulla of Vater

Takahashi,Nobuyasu; Aoyama,Fumiyo; Hiyoshi,Masahide; Kataoka,Hiroaki; Sawaguchi,Akira

doi:10.3892/ijo.2014.2282

Establishment and biological characterization of a novel cell line derived from hepatoid adenocarcinoma originated at the ampulla of Vater

Authors:
- Nobuyasu Takahashi
- Fumiyo Aoyama
- Masahide Hiyoshi
- Hiroaki Kataoka
- Akira Sawaguchi
View Affiliations

Affiliations: Department of Anatomy, Ultrastructural Cell Biology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan, Department of Surgical Oncology and Regulation of Organ Function, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan, Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan
Published online on: January 28, 2014 https://doi.org/10.3892/ijo.2014.2282
Pages: 1139-1145

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hepatoid adenocarcinoma is a rare gastrointestinal tumor and mostly reported in the stomach. Effective chemotherapy has yet to be developed to improve poor prognosis. The present study was undertaken to establish a useful cell line derived from a hepatoid adenocarcinoma, possibly leading to a new therapeutic strategy. The new human cell line VAT-39 was established from a metastatic lymph node of a 69-year-old Japanese male patient with hepatoid adenocarcinoma of the ampulla of Vater. The primary tumor and metastatic lymph node were composed of hepatoid adenocarcinoma cells exhibiting immunohistochemical reactivity for alpha-fetoprotein (AFP) and glypican-3 (GPC3). In the metastatic lymph node, Periodic acid-Schiff (PAS) staining clarified diffuse deposition of glycogen in the cytoplasm, indicating analogous characteristics to the primary hepatoid adenocarcinoma. Moreover, VAT-39 cells produced high levels of AFP in the cultured medium, and reverse-transcriptase polymerase chain reaction (RT-PCR) verified increased expression of GPC3 mRNA in this cell line. Further, we evaluated the sensitivity to major chemotherapeutic drugs against the bile duct cancer. Neither 5-fluorouracil nor gemcitabine showed particular sensitivity to this cell line. The tumorigenicity of the cultured cells was confirmed in athymic nude mice and the histological features of the explanted tumor were similar to the VAT-39 cell line. The present VAT-39 is the first hepatoid adenocarcinoma cell line that originates from the ampulla of Vater and it will be applicable for basic biological studies searching for new strategies of molecular targeted chemotherapy to this disease.

View Figures

View References

1.	Bourreille J, Metayer P, Sauger F, Matray F and Fondimare A: Existence of alpha fetoprotein during gastric-origin secondary cancer of the liver. Presse Med. 78:1277–1278. 1970.In French.
2.	Ishikura H, Kirimoto K, Shamoto M, et al: Hepatoid adenocarcinomas of the stomach. An analysis of seven cases. Cancer. 58:119–126. 1986. View Article : Google Scholar : PubMed/NCBI
3.	Lattes C, Carella R, Faggioli S, Gabusi E and Grigioni WF: Hepatoid adenocarcinoma of the rectum arising in ulcerative colitis: report of a case. Dis Colon Rectum. 43:105–108. 2000. View Article : Google Scholar : PubMed/NCBI
4.	Paner GP, Thompson KS and Reyes CV: Hepatoid carcinoma of the pancreas. Cancer. 88:1582–1589. 2000. View Article : Google Scholar : PubMed/NCBI
5.	Arnould L, Drouot F, Fargeot P, et al: Hepatoid adenocarcinoma of the lung: report of a case of an unusual alpha-fetoprotein-producing lung tumor. Am J Surg Pathol. 21:1113–1118. 1997. View Article : Google Scholar : PubMed/NCBI
6.	Motoyama T, Higuchi M and Taguchi J: Combined choriocarcinoma, hepatoid adenocarcinoma, small cell carcinoma and tubular adenocarcinoma in the oesophagus. Virchows Arch. 427:451–454. 1995. View Article : Google Scholar : PubMed/NCBI
7.	Gardiner GW, Lajoie G and Keith R: Hepatoid adenocarcinoma of the papilla of Vater. Histopathology. 20:541–544. 1992. View Article : Google Scholar : PubMed/NCBI
8.	Sinard J, Macleay L Jr and Melamed J: Hepatoid adenocarcinoma in the urinary bladder. Unusual localization of a newly recognized tumor type. Cancer. 73:1919–1925. 1994. View Article : Google Scholar : PubMed/NCBI
9.	Ishikura H, Ishiguro T, Enatsu C, et al: Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment. Cancer. 67:3051–3056. 1991. View Article : Google Scholar : PubMed/NCBI
10.	Devouassoux-Shisheboran M, Schammel DP and Tavassoli FA: Ovarian hepatoid yolk sac tumours: morphological, immunohistochemical and ultrastructural features. Histopathology. 34:462–469. 1999. View Article : Google Scholar : PubMed/NCBI
11.	Toyoda H, Hirai T and Ishii E: Alpha-fetoprotein producing uterine corpus carcinoma: a hepatoid adenocarcinoma of the endometrium. Pathol Int. 50:847–852. 2000. View Article : Google Scholar : PubMed/NCBI
12.	Shintaku M, Kariya M, Shime H and Ishikura H: Adenocarcinoma of the uterine cervix with choriocarcinomatous and hepatoid differentiation: report of a case. Int J Gynecol Pathol. 19:174–178. 2000. View Article : Google Scholar : PubMed/NCBI
13.	Kono K, Amemiya H, Sekikawa T, et al: Clinicopathologic features of gastric cancers producing alpha-fetoprotein. Dig Surg. 19:359–365. 2002. View Article : Google Scholar : PubMed/NCBI
14.	Takahashi Y, Mai M, Ogino T, Ueda H, Sawaguchi K and Ueno M: Clinicopathological study of AFP producing gastric cancer - significance of AFP in gastric cancer. Nihon Geka Gakkai Zasshi. 88:696–700. 1987.In Japanese.
15.	Chang YC, Nagasue N, Abe S, Taniura H, Kumar DD and Nakamura T: Comparison between the clinicopathologic features of AFP-positive and AFP-negative gastric cancers. Am J Gastroenterol. 87:321–325. 1992.
16.	Sekiguchi M, Fujii Y, Saito A, et al: Alpha-fetoprotein-producing gastric carcinoma: biological properties of a cultured cell line. J Gastroenterol. 30:589–598. 1995. View Article : Google Scholar : PubMed/NCBI
17.	Matsuda M, Watanabe A, Sawada H, et al: Establishment of an alpha-fetoprotein-producing cell line derived from gastric cancer. In Vitro Cell Dev Biol Anim. 35:555–557. 1999. View Article : Google Scholar : PubMed/NCBI
18.	Terashima M, Ikeda K, Maesawa C, et al: Establishment of an alpha-fetoprotein-producing gastric cancer cell line in serum-free media. Jpn J Cancer Res. 82:883–885. 1991. View Article : Google Scholar : PubMed/NCBI
19.	Takahashi Y, Ohta T and Mai M: Angiogenesis of AFP producing gastric carcinoma: correlation with frequent liver metastasis and its inhibition by anti-AFP antibody. Oncol Rep. 11:809–813. 2004.
20.	Sawaguchi A, McDonald KL and Forte JG: High-pressure freezing of isolated gastric glands provides new insight into the fine structure and subcellular localization of H⁺/K⁺-ATPase in gastric parietal cells. J Histochem Cytochem. 52:77–86. 2004. View Article : Google Scholar
21.	Sawaguchi A, Aoyama F, Ide S, Goto Y and Suganuma T: A new device for high-pressure freezing of cultured cell monolayer using 10-micron-thin stainless discs as both culture plate and specimen carrier. J Electron Micros. 57:203–206. 2008. View Article : Google Scholar
22.	Sawaguchi A, Aoyama F, Ide S and Suganuma T: Capsule-supporting ring: a new device for resin embedding of glass-mounted specimens. J Microsc. 234:113–117. 2009. View Article : Google Scholar : PubMed/NCBI
23.	Aoyama F, Sawaguchi A, Ide S, Kitamura K and Suganuma T: Exfoliation of gastric pit-parietal cells into the gastric lumen associated with a stimulation of isolated rat gastric mucosa in vitro: a morphological study by the application of cryotechniques. Histochem Cell Biol. 129:785–793. 2008. View Article : Google Scholar
24.	Terracciano LM, Glatz K, Mhawech P, et al: Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: an immunohistochemical and molecular study of eight cases. Am J Surg Pathol. 27:1302–1312. 2003. View Article : Google Scholar
25.	Muehlemann M, Miller KD, Dauphinee M and Mizejewski GJ: Review of growth inhibitory peptide as a biotherapeutic agent for tumor growth, adhesion, and metastasis. Cancer Metastasis Rev. 24:441–467. 2005. View Article : Google Scholar : PubMed/NCBI
26.	Nagai E, Ueyama T, Yao T and Tsuneyoshi M: Hepatoid adenocarcinoma of the stomach. A clinicopathologic and immunohistochemical analysis. Cancer. 72:1827–1835. 1993. View Article : Google Scholar : PubMed/NCBI
27.	Yorita K, Takahashi N, Takai H, et al: Prognostic significance of circumferential cell surface immunoreactivity of glypican-3 in hepatocellular carcinoma. Liver Int. 31:120–131. 2011. View Article : Google Scholar : PubMed/NCBI
28.	Hishinuma M, Ohashi KI, Yamauchi N, et al: Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma. Histopathology. 49:479–486. 2006. View Article : Google Scholar
29.	Morford LA, Davis C, Jin L, Dobierzewska A, Peterson ML and Spear BT: The oncofetal gene glypican 3 is regulated in the postnatal liver by zinc fingers and homeoboxes 2 and in the regenerating liver by alpha-fetoprotein regulator 2. Hepatology. 46:1541–1547. 2007. View Article : Google Scholar
30.	Nakano K, Orita T, Nezu J, et al: Anti-glypican 3 antibodies cause ADCC against human hepatocellular carcinoma cells. Biochem Biophys Res Commun. 378:279–284. 2009. View Article : Google Scholar : PubMed/NCBI
31.	Ishiguro T, Sugimoto M, Kinoshita Y, et al: Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer. Cancer Res. 68:9832–9838. 2008. View Article : Google Scholar : PubMed/NCBI