Display options
Share it on

Int J Clin Exp Med. 2010 Feb 22;3(1):69-83.

Primary cell lines: false representation or model system? a comparison of four human colorectal tumors and their coordinately established cell lines.

International journal of clinical and experimental medicine

Danielle M Pastor, Lisa S Poritz, Thomas L Olson, Christina L Kline, Leonard R Harris, Walter A Koltun, Vernon M Chinchilli, Rosalyn B Irby

PMID: 20369042 PMCID: PMC2848308

Abstract

Cultured cell lines have played an integral role in the study of tumor biology since the early 1900's. The purpose of this study is to evaluate colorectal cancer (CRC) cell lines with respect to progenitor tumors and assess whether these cells accurately and reliably represent the cancers from which they are derived. Primary cancer cell lines were derived from fresh CRC tissue. Tumorigenicity of cell lines was assessed by subcutaneous injection of cells into athymic mice and calculation of tumor volume after 3 weeks. DNA ploidy was evaluated by flow cytometry. Invasive ability of the lines was tested with the MATRIGEL invasion assay at 24 or 48 hours. Cells were assessed for the presence of Kirsten-Ras (K-Ras), p-53, deleted in colon cancer (DCC), and Src. Protein profiling of cells and tissue was performed by surface enhanced laser desorption/ionization-time of flight/mass spectroscopy. microRNA expression in cell and tumor tissue samples was evaluated by FlexmiR MicroRNA Assays. Four cell lines were generated from tumor tissue from patients with CRC and confirmed to be tumorigenic (mean tumor volume 158.46 mm(3)). Two cell lines were noted to be diploid; two were aneuploid. All cell lines invaded the MATRIGEL starting as early as 24 hours. K-Ras, p53, DCC, and Src expression were markedly different between cell lines and corresponding tissue. Protein profiling yielded weak-to-moderate correlations between cell samples and respective tissues of origin. Weak-to-moderate tau correlations for levels of expression of human microRNAs were found between cells and respective tissue samples for each of the four pairings. Although our primary CRC cell lines vary in their expression of several tumor markers and known microRNAs from their respective progenitor tumor tissue, they do not statistically differ in overall profiles. Characteristics are retained that deem these cell lines appropriate models of disease; however, data acquired through the use of cell culture may not always be a completely reliable representation of tumor activity in vivo.

Keywords: Cell culture; colorectal cancer; primary cell lines

References

  1. Cancer Res. 1986 Apr;46(4 Pt 2):1928-33 - PubMed
  2. BMC Biotechnol. 2008 Nov 27;8:90 - PubMed
  3. J Mol Diagn. 2008 Nov;10(6):513-9 - PubMed
  4. Cancer Genet Cytogenet. 1984 Apr;11(4):399-404 - PubMed
  5. Cancer Res. 1976 Dec;36(12):4562-9 - PubMed
  6. J Steroid Biochem Mol Biol. 1997 Aug;62(5-6):391-9 - PubMed
  7. Anal Biochem. 1995 Feb 10;225(1):163-4 - PubMed
  8. RNA. 2007 Oct;13(10):1668-74 - PubMed
  9. J Cell Sci. 2006 Apr 15;119(Pt 8):1477-82 - PubMed
  10. Cancer Res. 2002 May 1;62(9):2669-74 - PubMed
  11. Am J Physiol. 1992 Sep;263(3 Pt 1):G312-8 - PubMed
  12. Oncogene. 1997 Dec 18;15(25):3083-90 - PubMed
  13. Pharm Res. 2003 Feb;20(2):324-7 - PubMed
  14. Cancer Res. 1981 May;41(5):1751-6 - PubMed
  15. Tissue Cell. 2008 Apr;40(2):95-102 - PubMed
  16. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12357-62 - PubMed
  17. Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2052-7 - PubMed
  18. Nat Genet. 2005 Jul;37(7):766-70 - PubMed
  19. J Cell Sci. 1994 Jan;107 ( Pt 1):213-25 - PubMed
  20. Chin J Dig Dis. 2005;6(2):68-71 - PubMed
  21. J Pharm Sci. 1996 Mar;85(3):270-3 - PubMed
  22. Biotechniques. 2007 Nov;43(5):575, 577-8, 581-2 passim - PubMed
  23. Cell. 1990 Jun 1;61(5):759-67 - PubMed
  24. BMC Biotechnol. 2007 Jun 29;7:36 - PubMed
  25. Int J Mol Med. 2007 Mar;19(3):453-60 - PubMed
  26. Eur J Pharm Sci. 2004 Jan;21(1):77-86 - PubMed
  27. Oncology. 2003;65(1):60-71 - PubMed
  28. Drug Metab Dispos. 2002 Jan;30(1):4-6 - PubMed
  29. Pharm Res. 1997 Jun;14(6):757-62 - PubMed
  30. Biometrics. 1989 Mar;45(1):255-68 - PubMed
  31. Toxicol In Vitro. 2003 Oct-Dec;17(5-6):761-7 - PubMed

Publication Types