Skip to main content

Advertisement

SpringerLink
Log in

Establishment and Characterization of a High Metastatic Potential in the Peritoneum for Human Gastric Cancer by Orthotopic Tumor Cell Implantation

  • Original Paper
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The aim of this study was to establish an orthotopic implantation model with high metastasis of gastric cancer to the peritoneum which is more faithful to clinical metastasis. A human gastric carcinoma cell line, GC9811, was injected as a single-cell suspension into the stomach of nude mice. The cells from some peritoneum metastatic foci were expanded in vitro and subsequently implanted to the stomach wall of nude mice. By repeating the in vivo stepwise selection method for four rounds and cloning culture, we obtained a cell line designated GC9811-P, which developed peritoneal metastasis in 13 of 13 (100%) of mice, compared with only 20% of those implanted with parental GC9811. The metastatic foci in the peritoneum showed essentially the same histological appearance as those induced by parental cells. Tumor cell growth of GC9811-P in vitro was faster than that of GC9811. Motility assays demonstrated higher motility of GC9811-P than of GC9811. The adhesive ability of GC9811-P cells to laminin was lower than that of GC9811 cells, whereas the ability of GC9811-P cells to adhere to fibronectin was significantly higher than that of parental cells. Differences between GC9811-P and their parental GC9811 cells were found in expression levels of various molecules by flow cytometric and western blot. The findings indicated that up-regulation in the expressions of CD155, VEGF, syndecan-1, and syndecan-2 or down-regulation in the expressions of IL-6 and E-cadherin play an important role in the peritoneal metastasis of human gastric carcinoma cells. The high-metastatic cell line appears to be useful for investigating the mechanisms of peritoneal metastasis and preventing peritoneal metastasis of human gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Sporn MB (1996) The war on cancer. Lancet 347:1377–1381

    Article  PubMed  CAS  Google Scholar 

  2. Nagasako Y, Misawa K, Kohashi S, Hasegawa K, Okawa Y, Sano H, Takada A, Sato H (2003) Evaluation of malignancy using Ki-67 labeling index for gastric stromal tumor. Gastric Cancer 6:168–172

    Article  PubMed  Google Scholar 

  3. Maehara Y, Hasuda S, Koga T, Tokunaga E, Kakeji Y, Sugimachi K (2000) Postoperative outcome and sites of recurrence in patients following curative resection of gastric cancer. Br J Surg 87:353–357

    Article  PubMed  CAS  Google Scholar 

  4. Shono M, Sato N, Mizumoto K, Maehara N, Nakamura M, Nagai E, Tanaka M (2001) Stepwise progression of centrosome defects associated with local tumor growth and metastatic process of human pancreatic carcinoma cells transplanted orthotopically into nude mice. Lab Invest 81:945–952

    PubMed  CAS  Google Scholar 

  5. Yao X, Hu JF, Daniels M, Yien H, Lu H, Sharan H, Zhou X, Zeng Z, Li T, Yang Y, Hoffman AR (2003) A novel orthotopic tumor model to study growth factors and oncogenes in hepatocarcinogenesis. Clin Cancer Res 9:2719–2726

    PubMed  CAS  Google Scholar 

  6. Yashiro M, Chung YS, Nishimura S, Inoue T, Sowa M (1996) Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice. Clin Exp Metastasis 14:43–54

    Article  PubMed  CAS  Google Scholar 

  7. Yanagihara K, Takigahira M, Tanaka H, Komatsu T, Fukumoto H, Koizumi F, Nishio K, Ochiya T, Ino Y, Hirohashi S (2005) Development and biological analysis of peritoneal metastasis mouse models for human scirrhous stomach cancer. Cancer Sci 96:323–332

    Article  PubMed  CAS  Google Scholar 

  8. Hu S, Guo X, Xie H, Du Y, Pan Y, Shi Y, Wang J, Hong L, Han S, Zhang D, Huang D, Zhang K, Bai F, Jiang H, Zhai H, Nie Y, Wu K, Fan D (2006) Phage display selection of peptides that inhibit metastasis ability of gastric cancer cells with high liver-metastatic potential. Biochem Biophys Res Commun 341:964–972

    Article  PubMed  CAS  Google Scholar 

  9. FH Bai, Guo XN, Yang L, Zhai HH, Wu KC, Fan DM (2003) Establishment of transplantation of human gastric tumor metastasis model in nude mice. J Fourth Mil Med Univ 24:873–875

    Google Scholar 

  10. Yamaguchi K, Ura H, Yasoshima T, Shishido T, Denno R, Hirata K (2001) Liver metastatic Model for human gastric cancer established by orthotopic tumor cell implantation. World J Surg 25:131–137

    Article  PubMed  CAS  Google Scholar 

  11. Wang J, Wu K, Zhang D, Tang H, Xie H, Hong L, Pan Y, Lan M, Hu S, Ning X, Fan D (2005) Expressions and clinical significances of angiopoietin-1, -2 and Tie2 in human gastric cancer. Biochem Biophys Res Commun 337:386–393

    Article  PubMed  CAS  Google Scholar 

  12. Hippo Y, Yashiro M, Ishii M, Taniguchi H, Tsutsumi S, Hirakawa K, Kodama T, Aburatani H (2001) Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. Cancer Res 61:889–895

    PubMed  CAS  Google Scholar 

  13. Bouvet M, Wang J, Nardin SR, Nassirpour R, Yang M, Baranov E, Jiang P, Moossa AR, Hoffman RM (2002) Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model. Cancer Res 62:1534–1540

    PubMed  CAS  Google Scholar 

  14. Kondo K, Fujino H, Miyoshi T, Ishikura H, Sakiyama S, Monden Y (2004) Orthotopically implanted SCID mouse model of human lung cancer suitable for investigating metastatic potential and anticancer drug effects. Oncol Rep 12:991–999

    PubMed  CAS  Google Scholar 

  15. Hofmann HS, Hansen G, Richter G, Taege C, Simm A, Silber RE, Burdach S (2005) Matrix metalloproteinase-12 expression correlates with local recurrence and metastatic disease in non-small cell lung cancer patients. Clin Cancer Res 11:1086–1092

    PubMed  CAS  Google Scholar 

  16. Agnantis NJ, Goussia AC, Batistatou A, Stefanou D (2004) Tumor markers in cancer patients. An update of their prognostic significance. Part II. In Vivo 18:481–488

    CAS  Google Scholar 

  17. Rodriguez-Rodriguez L, Sancho-Torres I, Mesonero C, Gibbon DG, Shih WJ, Zotalis G (2003) The CD44 receptor is a molecular predictor of survival in ovarian cancer. Med Oncol 20:255–263

    Article  PubMed  CAS  Google Scholar 

  18. Katsura M, Furumoto H, Nishimura M, Kamada M, Aono T (1998) Overexpression of CD44 variants 6 and 7 in human endometrial cancer. Gynecol Oncol 71:185–189

    Article  PubMed  CAS  Google Scholar 

  19. Kikkawa H, Kaihou M, Horaguchi N, Uchida T, Imafuku H, Takiguchi A, Yamazaki Y, Koike C, Kuruto R, Kakiuchi T, Tsukada H, Takada Y, Matsuura N, Oku N (2002) Role of integrin alpha (v) beta3 in the early phase of liver metastasis: PET and IVM analyses. Clin Exp Metastasis 19:717–725

    Article  PubMed  CAS  Google Scholar 

  20. Arboleda MJ, Lyons JF, Kabbinavar FF, Bray MR, Snow BE, Ayala R, Danino M, Karlan BY, Slamon DJ (2003) Overexpression of AKT2/protein kinase B beta leads to up-regulation of beta1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells. Cancer Res 63:196–206

    PubMed  CAS  Google Scholar 

  21. Merrill MK, Bernhardt G, Sampson JH, Wikstrand CJ, Bigner DD, Gromeier M (2004) Poliovirus receptor CD155-targeted oncolysis of glioma. Neuro-oncol 6:208–217

    Article  PubMed  CAS  Google Scholar 

  22. Sloan KE, Eustace BK, Stewart JK, Zehetmeier C, Torella C, Simeone M (2004) CD155/PVR plays a key role in cell motility during tumor cell invasion and migration. BMC Cancer 4:73

    Article  PubMed  Google Scholar 

  23. Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611

    Article  PubMed  CAS  Google Scholar 

  24. McQuade KJ, Rapraeger AC (2003) Syndecan-1 transmembrane and extracellular domains have unique and distinct roles in cell spreading. J Biol Chem 278:46607–466015

    Article  PubMed  CAS  Google Scholar 

  25. Sanderson RD (2001) Heparan sulfate proteoglycans in invasion and metastasis. Semin Cell Dev Biol 12:89–98

    Article  PubMed  CAS  Google Scholar 

  26. Beauvais DM, Rapraeger AC (2004) Syndecans in tumor cell adhesion and signaling. Reprod Biol Endocrinol 2:3

    Article  PubMed  Google Scholar 

  27. Barbareschi M, Maisonneuve P, Aldovini D, Cangi MG, Pecciarini L, Angelo Mauri F, Veronese S, Caffo O, Lucenti A, Palma PD, Galligioni E, Doglioni C (2003) High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer 98:474–483

    Article  PubMed  Google Scholar 

  28. Burbach BJ, Friedl A, Mundhenke C, Rapraeger AC (2003) Syndecan-1 accumulates in lysosomes of poorly differentiated breast carcinoma cells. Matrix Biol 22:163–177

    Article  PubMed  CAS  Google Scholar 

  29. Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, Lander AD, Korc M (2001) Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Res 61:5562–5569

    PubMed  CAS  Google Scholar 

  30. Keller ET, Wanagat J, Ershler WB (1996) Molecular and cellular biology of interleukin-6 and it receptor. Front Biosci 1: 340–357

    Google Scholar 

  31. Mayer B, Johnson JP, Leitl F, Jauch KW, Heiss MM, Schildberg FW, Birchmeier W, Funke I (1993) E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res 53:1690–1695

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Grant 30160033 from the National Natural Science Foundation of China. We also thank Taidong Qiao for excellent technical assistance.

Author information

Authors and Affiliations

  1. State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, XiJing Hospital, The Fourth Military Medical University, Xi’an, 710032, ShaanXi Province, China

    Feihu Bai, Jun Wang, Yongquan Shi, Faming Zhang, Huihong Zhai, Yuanyuan Lu, Huahong Xie, Kaichun Wu & Daiming Fan

  2. Department of Gastroenterology, The Affiliated Hospital of Ninxia Medical College, Yinchuan, Ningxia Hui Autonomous Region Province, 750004, China

    Feihu Bai, Xinning Guo & Li Yang

Authors
  1. Feihu Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinning Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongquan Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Faming Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Huihong Zhai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuanyuan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Huahong Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kaichun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Daiming Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daiming Fan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bai, F., Guo, X., Yang, L. et al. Establishment and Characterization of a High Metastatic Potential in the Peritoneum for Human Gastric Cancer by Orthotopic Tumor Cell Implantation. Dig Dis Sci 52, 1571–1578 (2007). https://doi.org/10.1007/s10620-006-9570-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9570-x

Keywords

Search

Navigation