Skip to main content
SpringerLink
Log in
Book cover

Pancreatic Cancer pp 457–469Cite as

Molecular Characterization of Pancreatic Cancer Cell Lines

  • Reference work entry

Abstract:

A Relatively large number of very well characterized human pancreatic cancer cell lines is available for preclinical investigation. However, there is a perception that continuous passage in tissue culture coupled with genomic instability has made them poor models of human disease and that preclinical attempts to identify active therapeutic regimens that employed them as models have uniformly failed when they were translated into clinical trials. Here we will review the current status of some high profile studies employing cell lines to model human cancer biology and identify the potential strengths and weaknesses associated with the approach. We will also discuss results that challenge the notion that cell lines are poor models of human cancer biology.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   649.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Frese KK, Tuveson DA: Maximizing mouse cancer models. Nat Rev Cancer 2007;7(9):645–658.

    Article  CAS  PubMed  Google Scholar 

  2. Olive KP, Tuveson DA: The use of targeted mouse models for preclinical testing of novel cancer therapeutics. Clin Cancer Res 2006;12(18):5277–5287.

    Article  CAS  PubMed  Google Scholar 

  3. Embuscado EE, Laheru D, Ricci F, et al.: Immortalizing the complexity of cancer metastasis: genetic features of lethal metastatic pancreatic cancer obtained from rapid autopsy. Cancer Biol Ther 2005;4(5):548–554.

    Article  CAS  PubMed  Google Scholar 

  4. Li C, Heidt DG, Dalerba P, et al.: Identification of pancreatic cancer stem cells. Cancer Res 2007;67(3):1030–1037.

    Article  CAS  PubMed  Google Scholar 

  5. Yauch RL, Gould SE, Scales SJ, et al.: A paracrine requirement for hedgehog signalling in cancer. Nature 2008;455(7211):406–410.

    Article  CAS  PubMed  Google Scholar 

  6. Scherer WF, Syverton JT, Gey GO: Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J Exp Med 1953;97(5):695–710.

    Article  CAS  PubMed  Google Scholar 

  7. Lieber M, Mazzetta J, Nelson-Rees W, Kaplan M, Todaro G: Establishment of a continuous tumor-cell line (panc-1) from a human carcinoma of the exocrine pancreas. Int J Cancer 1975;15(5):741–747.

    Article  CAS  PubMed  Google Scholar 

  8. Yunis AA, Arimura GK, Russin DJ: Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase. Int J Cancer 1977;19(1):128–135.

    Article  CAS  PubMed  Google Scholar 

  9. Logsdon CD, Simeone DM, Binkley C, et al.: Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res 2003;63(10):2649–2657.

    CAS  PubMed  Google Scholar 

  10. Neve RM, Chin K, Fridlyand J, et al.: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006;10(6):515–527.

    Article  CAS  PubMed  Google Scholar 

  11. Hwang RF, Moore T, Arumugam T, et al.: Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Res 2008;68(3):918–926.

    Article  CAS  PubMed  Google Scholar 

  12. Yauch RL, Januario T, Eberhard DA, et al.: Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin Cancer Res 2005;11(24 Pt 1):8686–8698.

    Article  CAS  PubMed  Google Scholar 

  13. Barr S, Thomson S, Buck E, et al.: Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clin Exp Metastasis 2008;25(6):685–693.

    Article  PubMed  Google Scholar 

  14. Fuchs BC, Fujii T, Dorfman JD, et al.: Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res 2008;68(7):2391–2399.

    Article  CAS  PubMed  Google Scholar 

  15. Haddad Y, Choi W, McConkey DJ: Delta-crystallin enhancer binding factor 1 controls the epithelial to mesenchymal transition phenotype and resistance to the epidermal growth factor receptor inhibitor erlotinib in human head and neck squamous cell carcinoma lines. Clin Cancer Res 2009;15(2):532–542.

    Article  CAS  PubMed  Google Scholar 

  16. Pino MS, Balsamo M, Di Modugno F, et al.: Human Mena+11a isoform serves as a marker of epithelial phenotype and sensitivity to epidermal growth factor receptor inhibition in human pancreatic cancer cell lines. Clin Cancer Res 2008;14(15):4943–4950.

    Article  CAS  PubMed  Google Scholar 

  17. Thomson S, Buck E, Petti F, et al.: Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 2005;65(20):9455–9462.

    Article  CAS  PubMed  Google Scholar 

  18. Frederick BA, Helfrich BA, Coldren CD, et al.: Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma. Mol Cancer Ther 2007;6(6):1683–1691.

    Article  CAS  PubMed  Google Scholar 

  19. Black PC, Brown GA, Inamoto T, et al.: Sensitivity to epidermal growth factor receptor inhibitor requires E-cadherin expression in urothelial carcinoma cells. Clin Cancer Res 2008;14(5):1478–1486.

    Article  CAS  PubMed  Google Scholar 

  20. Shrader M, Pino MS, Brown G, et al.: Molecular correlates of gefitinib responsiveness in human bladder cancer cells. Mol Cancer Ther 2007;6(1):277–285.

    Article  CAS  PubMed  Google Scholar 

  21. Lee JK, Havaleshko DM, Cho H, et al.: A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery. Proc Natl Acad Sci USA 2007;104(32):13086–13091.

    Article  CAS  PubMed  Google Scholar 

  22. Havaleshko DM, Cho H, Conaway M, et al.: Prediction of drug combination chemosensitivity in human bladder cancer. Mol Cancer Ther 2007;6(2):578–586.

    Article  CAS  PubMed  Google Scholar 

  23. Lin WM, Baker AC, Beroukhim R, et al.: Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res 2008;68(3):664–673.

    Article  CAS  PubMed  Google Scholar 

  24. Adjei AA, Cohen RB, Franklin W, et al.: Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol 2008;26(13):2139–2146.

    Article  CAS  PubMed  Google Scholar 

  25. Wagner KW, Punnoose EA, Januario T, et al.: Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 2007;13(9):1070–1077.

    Article  CAS  PubMed  Google Scholar 

  26. Shoemaker RH: The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer 2006;6(10):813–823.

    Article  CAS  PubMed  Google Scholar 

  27. Johnson JI, Decker S, Zaharevitz D, et al.: Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer 2001;84(10):1424–1431.

    Article  CAS  PubMed  Google Scholar 

  28. Adams J, Palombella VJ, Sausville EA, et al.: Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999;59(11):2615–2622.

    CAS  PubMed  Google Scholar 

  29. McConkey DJ, Zhu K: Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist Updat 2008;11(4–5):164–179.

    Article  CAS  PubMed  Google Scholar 

  30. Davis DW, Buchholz TA, Hess KR, Sahin AA, Valero V, McConkey DJ: Automated quantification of apoptosis after neoadjuvant chemotherapy for breast cancer: early assessment predicts clinical response. Clin Cancer Res 2003;9(3):955–960.

    CAS  PubMed  Google Scholar 

  31. Hruban RH, Goggins M, Parsons J, Kern SE: Progression model for pancreatic cancer. Clin Cancer Res 2000;6(8):2969–2972.

    CAS  PubMed  Google Scholar 

  32. Jones S, Zhang X, Parsons DW, et al.: Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008;321(5897):1801–1806.

    Article  CAS  PubMed  Google Scholar 

  33. Pino MS, Shrader M, Baker CH, et al.: Transforming growth factor alpha expression drives constitutive epidermal growth factor receptor pathway activation and sensitivity to gefitinib (Iressa) in human pancreatic cancer cell lines. Cancer Res 2006;66(7):3802–3812.

    Article  CAS  PubMed  Google Scholar 

  34. Peinado H, Olmeda D, Cano A: Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 2007;7(6):415–428.

    Article  CAS  PubMed  Google Scholar 

  35. Witta SE, Gemmill RM, Hirsch FR, et al.: Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 2006;66(2):944–950.

    Article  CAS  PubMed  Google Scholar 

  36. Sausville EA, Burger AM: Contributions of human tumor xenografts to anticancer drug development. Cancer Res 2006;66(7):3351–3354, discussion 4.

    Article  CAS  PubMed  Google Scholar 

  37. Bruns CJ, Harbison MT, Kuniyasu H, Eue I, Fidler IJ: In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice. Neoplasia 1999;1(1):50–62.

    Article  CAS  PubMed  Google Scholar 

  38. Nakamura T, Fidler IJ, Coombes KR: Gene expression profile of metastatic human pancreatic cancer cells depends on the organ microenvironment. Cancer Res 2007;67(1):139–148.

    Article  CAS  PubMed  Google Scholar 

  39. Khanbolooki S, Nawrocki ST, Arumugam T, et al.: Nuclear factor-kappaB maintains TRAIL resistance in human pancreatic cancer cells. Mol Cancer Ther 2006;5(9):2251–2260.

    Article  CAS  PubMed  Google Scholar 

  40. Pan X, Arumugam T, Yamamoto T, et al.: Nuclear factor-kappaB p65/relA silencing induces apoptosis and increases gemcitabine effectiveness in a subset of pancreatic cancer cells. Clin Cancer Res 2008;14(24):8143–8151.

    Article  CAS  PubMed  Google Scholar 

  41. Nawrocki ST, Bruns CJ, Harbison MT, et al.: Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther 2002;1(14):1243–1253.

    CAS  PubMed  Google Scholar 

  42. Nawrocki ST, Carew JS, Pino MS, et al.: Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. Cancer Res 2005;65(24):11658–11666.

    Article  CAS  PubMed  Google Scholar 

  43. Nawrocki ST, Sweeney-Gotsch B, Takamori R, McConkey DJ: The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther 2004;3(1):59–70.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Cancer Biology, Urology, and Surgical Oncology, U.T. M.D. Anderson Cancer Center, Houston, TX, USA

    David J. McConkey, Woonyoung Choi, Keith Fournier, Lauren Marquis, Vijaya Ramachandran & Thiruvengadam Arumugam

Authors
  1. David J. McConkey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Woonyoung Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keith Fournier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lauren Marquis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vijaya Ramachandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thiruvengadam Arumugam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J. McConkey .

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this entry

Cite this entry

McConkey, D.J., Choi, W., Fournier, K., Marquis, L., Ramachandran, V., Arumugam, T. (2010). Molecular Characterization of Pancreatic Cancer Cell Lines. In: Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77498-5_19

Download citation

Publish with us

Policies and ethics

Search

Navigation