Open Access

Characterization of human gastric adenocarcinoma cell lines established from peritoneal ascites

  • Authors:
    • Bożenna Mytar
    • Małgorzata Stec
    • Rafał Szatanek
    • Kazimierz Węglarczyk
    • Katarzyna Szewczyk
    • Antoni Szczepanik
    • Grażyna Drabik
    • Jarek Baran
    • Maciej Siedlar
    • Monika Baj‑Krzyworzeka
  • View Affiliations

  • Published online on: February 8, 2018     https://doi.org/10.3892/ol.2018.7995
  • Pages: 4849-4858
  • Copyright: © Mytar et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

The three cell lines, designated as gastric cancer (GC)1401, GC1415 and GC1436 were derived from peritoneal effusions from patients with gastric adenocarcinoma. Cell lines were established in tissue culture and in immunodeficient, non‑obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. All cell lines were cultured in Dulbecco's modified Eagle's medium supplemented with 5% fetal bovine serum. These cell lines were grown as an adherent monolayer with doubling time ranging between 25 h (GC1436 cell line) and 30‑34 h (GC1401 and GC1415, respectively). All cells showed morphological features of epithelial‑like cells, forming sheets of polygonal cells. Chromosomal analysis showed that the modal numbers ranged from 52 (GC1401), 51‑56 (GC1415) and 106 (GC1436). High heterogeneity, resulting from several structural and numerical chromosomal abnormalities were evident in all cell lines. The surface marker expression suggested a tumor origin of the cells, and indicated the intestinal phenotype of a GC (CD10+, MUC1). All three cell lines were tumorigenic but not metastatic, in vivo, in NOD/SCID mice. The lack of metastatic potential was suggested by the lack of aldehyde dehydrogenase 1A1 activity. In conclusion, these newly established GC cell lines widen the feasibility of the functional studies on biology of GC as well as drug testing for potential therapeutic purposes.

References

1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Verdecchia A, Santaquilani M and Sant M: Survival for cancer patients in Europe. Ann Ist Super Sanita. 45:315–324. 2009.PubMed/NCBI

3 

Fidler IJ: Biological heterogeneity of cancer: Implication to therapy. Hum Vaccines Immunother. 8:1141–1142. 2012. View Article : Google Scholar

4 

Kato M, Shimada Y, Tanaka H, Hosotani R, Ohshio G, Ishizaki K and Imamura M: Characterization of six cell lines established from human pancreatic adenocarcinomas. Cancer. 85:832–840. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Park JG, Frucht H, LaRocca RV, Bliss DP Jr, Kurita Y, Chen TR, Henslee JG, Trepel JB, Jensen RT, Johnson BE, et al: Characteristics of cell lines established from human gastric carcinoma. Cancer Res. 50:2773–2780. 1990.PubMed/NCBI

6 

Chun YH, Kil JI, Suh YS, Kim SH, Kim H and Park SH: Characterization of chromosomal aberrations in human gastric carcinoma cell lines using chromosome painting. Cancer Genet Cytogenet. 119:18–25. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Croker AK, Goodale D, Chu J, Postenka C, Hedley BD, Hess DA and Allan AL: High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med. 13:2236–2252. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Liao J, Qian F, Tchabo N, Mhawech-Fauceglia P, Beck A, Qian Z, Wang X, Huss WJ, Lele SB, Morrison CD and Odunsi K: Ovarian cancer spheroid cells with stem cell-like properties contribute to tumor generation, metastasis and chemotherapy resistance through hypoxia-resistant metabolism. PLoS One. 9:e849412014. View Article : Google Scholar : PubMed/NCBI

9 

Mu X, Patel S, Mektepbayeva D, Mahjoub A, Huard J and Weiss K: Retinal targets ALDH positive cancer stem cell and alters the phenotype of highly metastatic osteosarcoma cells. Sarcoma. 2015:7849542015. View Article : Google Scholar : PubMed/NCBI

10 

Ajani JA, Wang X, Song S, Suzuki A, Taketa T, Sudo K, Wadhwa R, Hofstetter WL, Komaki R, Maru DM, et al: ALDH-1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients. Mol Oncol. 8:142–149. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Li XS, Xu Q, Fu XY and Luo WS: ALDH1A1 overexpression is associated with the progression and prognosis in gastric cancer. BMC Cancer. 14:7052014. View Article : Google Scholar : PubMed/NCBI

12 

Schafer LG, McGowan-Jordan J and Schmid M: ISCN 2013 An International System for Human Cytogenetic Nomenclature. S. Karger; Basel: 2013

13 

Szatanek R, Drabik G, Baran J, Kolodziejczyk P, Kulig J, Stachura J and Zembala M: Detection of isolated tumor cells in the blood and bone marrow of patients with gastric cancer by combined sorting, isolation and determination of MAGE-1, −2 mRNA expression. Oncol Rep. 19:1055–1060. 2008.PubMed/NCBI

14 

Iwanuma Y, Chen FA, Egilmez NK, Takita H and Bankert RB: Antitumor immune response of human peripheral blood lymphocytes coengrafted with tumor into severe combined immunodeficient mice. Cancer Res. 57:2937–2942. 1997.PubMed/NCBI

15 

Alama A, Barbieri F, Favre A, Cagnoli M, Noviello E, Pedullà F, Viale M, Foglia G and Ragni N: Establishment and characterization of three new cell lines derived from the ascites of human ovarian carcinomas. Gynecol Oncol. 62:82–88. 1996. View Article : Google Scholar : PubMed/NCBI

16 

Birsoy K, Possemato R, Lorbeer FK, Bayraktar EC, Thiru P, Yucel B, Wang T, Chen WW, Clish CB and Sabatini DM: Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. Nature. 508:108–112. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Doak SH: Aneuploidy in upper gastro-intestinal tract cancers-a potential prognostic marker? Mutat Res. 651:93–104. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Leal MF, Martins do Nascimento JL, da Silva CE, Vita Lamarão MF, Calcagno DQ, Khayat AS, Assumpção PP, Cabral IR, de Arruda Cardoso Smith M and Burbano RR: Establishment and conventional cytogenetic characterization of three gastric cancer cell lines. Cancer Genet Cytogenet. 195:85–91. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Buffart TE, Carvalho B, Mons T, Reis RM, Moutinho C, Silva P, van Grieken NC, Vieth M, Stolte M, van de Velde CJ, et al: DNA copy number profiles of gastric cancer precursor lesions. BMC Genomics. 8:3452007. View Article : Google Scholar : PubMed/NCBI

20 

David S and Meltzer SJ: Stomach-genetic and epigenetic alterations of preneoplastic and neoplastic lesions. Cancer Biomark. 9:493–507. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Kimura Y, Noguchi T, Kawahara K, Kashima K, Daa T and Yokoyama S: Genetic alterations in 102 primary gastric cancers by comparative genomic hybridization: Gain of 20q and loss of 18q are associated with tumor progression. Mod Pathol. 17:1328–1337. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Wu CW, Chen GD, Fann CS, Lee AF, Chi CW, Liu JM, Weier U and Chen JY: Clinical implications of chromosomal abnormalities in gastric adenocarcinomas. Genes Chromosom Cancer. 35:219–231. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Koo SH, Kwon KC, Shin SY, Jeon YM, Park JW, Kim SH and Noh SM: Genetic alterations of gastric cancer: Comparative genomic hybridization and fluorescence In situ hybridization studies. Cancer Genet Cytogenet. 117:97–103. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Sakakura C, Hagiwara A, Taniguchi H, Yamaguchi T, Yamagishi H, Takahashi T, Koyama K, Nakamura Y, Abe T and Inazawa J: Chromosomal aberrations in human hepatocellular carcinomas associated with hepatitis C virus infection detected by comparative genomic hybridization. Br J Cancer. 80:2034–2039. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Stocks S, Pratt N, Sales M, Johnston DA, Thompson AM, Carey FA and Kernohan NM: Chromosomal imbalances in gastric and esophageal adenocarcinoma: Specific comparative genomic hybridization-detected abnormalities segregate with junctional adenocarcinomas. Genes Chromosomes Cancer. 32:50–58. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Göhring G, Michalova K, Beverloo HB, Betts D, Harbott J, Haas OA, Kerndrup G, Sainati L, Bergstraesser E, Hasle H, et al: Complex karyotype newly defined: The strongest prognostic factor in advanced childhood myelodysplastic syndrome. Blood. 116:3766–3769. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Orozco JJ and Appelbaum FR: Unfavorable, complex, and monosomal karyotypes: The most challenging forms of acute myeloid leukemia. Oncology (Williston Park). 26:706–712. 2012.PubMed/NCBI

28 

Höglund M, Frigyesi A, Säll T, Gisselsson D and Mitelman F: Statistical behavior of complex cancer karyotypes. Genes Chromosomes Cancer. 42:327–341. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Sakakura C, Hagiwara A, Nakanishi M, Shimomura K, Takagi T, Yasuoka R, Fujita Y, Abe T, Ichikawa Y, Takahashi S, et al: Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites. Brit J Cancer. 87:1153–1161. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Washington K, Gottried MR and Telen MJ: Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas. Hum Pathol. 25:1043–1049. 1994. View Article : Google Scholar : PubMed/NCBI

31 

Yamaguchi K, Ura H, Yasoshima T, Shishido T, Denno R and Hirata K: Establishment and characterization of a human gastric carcinoma cell line that is highly metastatic to lymph nodes. J Exp Clin Cancer Res. 19:113–120. 2000.PubMed/NCBI

32 

Mayer B, Lorenz C, Babic R, Jauch KW, Schildberg FW, Funke I and Johnson JP: Expression of leukocyte cell adhesion molecules on gastric carcinomas: Possible involvement of LFA-3 expression in the development of distant metastases. Int J Cancer. 64:415–423. 1995. View Article : Google Scholar : PubMed/NCBI

33 

Wakatsuki K, Yamada Y, Narikiyo M, Ueno M, Takayama T, Tamaki H, Miki K, Matsumoto S, Enomoto K, Yokotani T and Nakajima Y: Clinicopathological and prognostic significance of mucin phenotype in gastric cancer. J Surg Oncol. 98:124–129. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Xin Y, Grace A, Gallagher MM, Curran BT, Leader MB and Kay EW: CD44V6 in gastric carcinoma: A marker of tumor progression. Appl Immunohistochem Mol Morphol. 9:138–142. 2001. View Article : Google Scholar : PubMed/NCBI

35 

Chen J, Zhou J, Lu J, Xiong H, Shi X and Gong L: Significance of CD44 expression in head and neck cancer: A systemic review and meta-analysis. BMC Cancer. 14:152014. View Article : Google Scholar : PubMed/NCBI

36 

Ohtani H, Nakayama T and Yoshie O: In situ expression of the CCL20-CCR6 axis in lymphocyte-rich gastric cancer and its potential role in the formation of lymphoid stroma. Pathol Int. 61:645–651. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Arigami T, Natsugoe S, Uenosono Y, Yanagita S, Arima H, Hirata M, Ishigami S and Aikou T: CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer. Int J Oncol. 35:19–24. 2009. View Article : Google Scholar : PubMed/NCBI

38 

Jöhrer K, Zelle-Rieser C, Perathoner A, Moser P, Hager M, Ramoner R, Gander H, Höltl L, Bartsch G, Greil R and Thurnher M: Up-regulation of functional chemokine receptor CCR3 in human renal cell carcinoma. Clin Cancer Res. 11:2459–2465. 2005. View Article : Google Scholar : PubMed/NCBI

39 

Rubie C, Oliveira V, Kempf K, Wagner M, Tilton B, Rau B, Kruse B, Konig J and Schilling M: Involvement of chemokine receptor CCR6 in colorectal cancer metastasis. Tumor Biol. 27:166–174. 2006. View Article : Google Scholar

40 

Koizumi K, Hojo S, Akashi T, Yasumoto K and Saiki I: Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response. Cancer Sci. 98:1652–1658. 2007. View Article : Google Scholar : PubMed/NCBI

41 

Sugasawa H, Ichikura T, Tsujimoto H, Kinoshita M, Morita D, Ono S, Chochi K, Tsuda K, Seki S and Mochizuki H: Prognostic significnce of expression of CCL5/RANTES receptors in patients with gastric cancer. J Surg Oncol. 97:445–450. 2008. View Article : Google Scholar : PubMed/NCBI

42 

Yang Y, Du L, Yang X, Qu A, Zhang X, Zhou C and Wang C: Aberrant CCR4 expression is involved in tumor invasion of lymph node-negative human gastric cancer. PLoS One. 10:e01200592015. View Article : Google Scholar : PubMed/NCBI

43 

Carl-McGrath S, Lendeckel U, Ebert M, Wolter AB, Roessner A and Röcken C: The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer. Int J Oncol. 25:1223–1232. 2004.PubMed/NCBI

44 

Namikawa T and Hanazaki K: Mucin phenotype of gastric cancer and clinicopathology of gastric-type differentiated adenocarcinoma. World J Gastroenterol. 16:4634–4639. 2010. View Article : Google Scholar : PubMed/NCBI

45 

Barresi V, Vitarelli E, Grosso M, Tuccari G and Barresi G: Relationship between immunoexpression of mucin peptide cores MUC1 and MUC2 and Lauren's histologic subtypes of gastric carcinomas. Eur J Histochem. 50:301–309. 2006.PubMed/NCBI

46 

Yalcin S, Yildiz Y and Sokmensuer C: Frequency of c-Met, HGF, and HER-2 expression and evaluation of their association with clinicopathologic and prognostic factors in gastric cancer. J Clin Oncol. 33 3 Suppl:S882015. View Article : Google Scholar

47 

Teng L and Lu J: cMET as a potential therapeutic target in gastric cancer (Review). Int J Mol Med. 32:1247–1254. 2013. View Article : Google Scholar : PubMed/NCBI

48 

Zhu GJ, Xu CW, Fang MY, Zhang YP and Li Y: Detection of Her2/neu expression in gastric cancer: Quantitative PCR versus immunohistochemistry. Exp Ther Med. 8:1501–1507. 2014. View Article : Google Scholar : PubMed/NCBI

49 

Zheng HC, Takahashi H, Murai Y, Zui ZG, Nomoto K, Miwa S, Tsuneyama K and Takano Y: Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: A good marker for local invasion and prognosis. Br J Cancer. 95:1371–1378. 2006. View Article : Google Scholar : PubMed/NCBI

50 

Fidler IJ: Critical factors in the biology of human cancer metastasis: Twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res. 50:6130–6138. 1990.PubMed/NCBI

51 

Sharkey FE and Fogh J: Metastasis of human tumors in athymic nude mice. Int J Cancer. 24:733–738. 1979. View Article : Google Scholar : PubMed/NCBI

52 

Zheng MJ, Wang J, Chen YW, Xu L, Xue DD, Fu W, Zhang YF, Du Q, Zhao Y, Ling LJ, et al: A novel mouse model of gastric cancer with human gastric microenvironment. Cancer Lett. 325:108–115. 2012. View Article : Google Scholar : PubMed/NCBI

53 

Kyriazis AP, DiPersio L, Michael GJ, Pesce AJ and Stinnett JD: Growth patterns and metastatic behavior of human tumors growing in athymic mice. Cancer Res. 38:3186–3190. 1978.PubMed/NCBI

54 

Chen T, Yang K, Yu J, Meng W, Yuan D, Bi F, Liu F, Liu J, Dai B, Chen X, et al: Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients. Cell Res. 22:248–258. 2012. View Article : Google Scholar : PubMed/NCBI

55 

Wakamatsu Y, Sakamoto N, Oo HZ, Naito Y, Uraoka N, Anami K, Sentani K, Oue N and Yasui W: Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int. 62:112–119. 2012. View Article : Google Scholar : PubMed/NCBI

56 

Wu S, Xue W, Huang X, Yu X, Luo M, Huang Y, Liu Y, Bi Z, Qiu X and Bai S: Distinct prognostic values of ALDH1 isoenzymes in breast cancer. Tumor Biol. 36:2421–2426. 2015. View Article : Google Scholar

57 

You Q, Guo H and Xu D: Distinct prognostic values and potential drug targets of ALDH1 isoenzymes in non-small-cell lung cancer. Drug Des Devel Ther. 9:5087–5097. 2015. View Article : Google Scholar : PubMed/NCBI

58 

Jia J, Parikh H, Xiao W, Hoskins JW, Pflicke H, Liu X, Collins I, Zhou W, Wang Z, Powell J, et al: An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer. BMC Med Genomics. 6:332013. View Article : Google Scholar : PubMed/NCBI

59 

Kong B, Wu W, Cheng T, Schlitter AM, Qian C, Bruns P, Jian Z, Jäger C, Regel I, Raulefs S, et al: A subset of metastatic pancreatic ductal adenocarcinomas depends quantitatively on oncogenic Kras/Mek/Erk-induced hyperactive mTOR signalling. Gut. 65:647–657. 2016. View Article : Google Scholar : PubMed/NCBI

60 

Saw YT, Yang J, Ng SK, Liu S, Singh S, Singh M, Welch WR, Tsuda H, Fong WP, Thompson D, et al: Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures. BMC Cancer. 12:3292012. View Article : Google Scholar : PubMed/NCBI

61 

Mao P, Joshi K, Li J, Kim SH, Li P, Santana-Santos L, Luthra S, Chandran UR, Benos PV, Smith L, et al: Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3. Proc Natl Acad Sci USA. 110:pp. 8644–8649. 2013; View Article : Google Scholar : PubMed/NCBI

62 

Li K, Guo X, Wang Z, Li X, Bu Y, Bai X, Zheng L and Huang Y: The prognostic roles of ALDH1 isoenzymes in gastric cancer. Onco Targets Ther. 9:3405–3414. 2016.PubMed/NCBI

63 

Goedde HW and Agarwal DP: Pharmacogenetics of aldehyde dehydrogenase (ALDH). Pharmacol Ther. 45:345–371. 1990. View Article : Google Scholar : PubMed/NCBI

64 

Hidaka A, Sasazuki S, Matsuo K, Ito H, Sawada N, Shimazu T, Yamaji T, Iwasaki M, Inoue M and Tsugane S; JPHC Study Group, : Genetic polymorphisms of ADH1B, ADH1C and ALDH2, alcohol consumption, and the risk of gastric cancer: The Japan Public Health Center-based prospective study. Carcinogenesis. 36:223–231. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

April 2018
Volume 15 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Mytar, B., Stec, M., Szatanek, R., Węglarczyk, K., Szewczyk, K., Szczepanik, A. ... Baj‑Krzyworzeka, M. (2018). Characterization of human gastric adenocarcinoma cell lines established from peritoneal ascites. Oncology Letters, 15, 4849-4858. https://doi.org/10.3892/ol.2018.7995
MLA
Mytar, B., Stec, M., Szatanek, R., Węglarczyk, K., Szewczyk, K., Szczepanik, A., Drabik, G., Baran, J., Siedlar, M., Baj‑Krzyworzeka, M."Characterization of human gastric adenocarcinoma cell lines established from peritoneal ascites". Oncology Letters 15.4 (2018): 4849-4858.
Chicago
Mytar, B., Stec, M., Szatanek, R., Węglarczyk, K., Szewczyk, K., Szczepanik, A., Drabik, G., Baran, J., Siedlar, M., Baj‑Krzyworzeka, M."Characterization of human gastric adenocarcinoma cell lines established from peritoneal ascites". Oncology Letters 15, no. 4 (2018): 4849-4858. https://doi.org/10.3892/ol.2018.7995