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Article

Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition

  • Authors:
    • Karl Quint
    • Manuel Tonigold
    • Pietro Di Fazio
    • Roberta Montalbano
    • Susanne Lingelbach
    • Felix Rückert
    • Beate Alinger
    • Matthias Ocker
    • Daniel Neureiter
  • View Affiliations / Copyright

    Affiliations: Institute for Surgical Research, Philipps University of Marburg, D-35043 Marburg, Germany, Department of Surgery, University Clinic Mannheim, D-68167 Mannheim, Germany, Institute of Pathology, Paracelsus Private Medical University, A-5020 Salzburg, Austria
  • Pages: 2093-2102
    |
    Published online on: October 1, 2012
       https://doi.org/10.3892/ijo.2012.1648
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Abstract

Objective response rates to standard chemotherapeutic regimens remain low in pancreatic cancer. Subpopulations of cells have been identified in various solid tumors which express stem cell-associated markers and are associated with increased resistance against radiochemotherapy. We investigated the expression of stem cell genes and markers of epithelial-mesenchymal transition in pancreatic cancer cells that survived high concentrations of gemcitabine treatment. Capan-1 and Panc-1 cells were continuously incubated with 1 and 10 µM gemcitabine. Surviving cells were collected after 1, 3 and 6 days. Expression of PDX-1, SHH, CD24, CD44, CD133, EpCAM, CBX7, OCT4, SNAIL, SLUG, TWIST, Ki-67, E-cadherin, β-catenin and vimentin were quantified by qPCR or immunocytochemistry. Migration was assessed by wound‑healing assay. SHH was knocked down using RNA interference. Five primary pancreatic cancer cell lines were used to validate the qPCR results. All investigated genes were upregulated after 6 days of gemcitabine incubation. Highest relative expression levels were observed for OCT4 (13.4-fold), CD24 (47.3-fold) and EpCAM (15.9-fold) in Capan-1 and PDX-1 (13.3‑fold), SHH (24.1-fold), CD44 (17.4-fold), CD133 (20.2-fold) and SLUG (15.2-fold) in Panc-1 cells. Distinct upregulation patterns were observed in the primary cells. Migration was increased in Panc-1 cells and changes in the expression of E-cadherin and β-catenin were typical of epithelial-mesenchymal transition in both cell lines. SHH knockdown reduced IC50 from 30.1 to 27.6 nM in Capan-1 while it strongly inhibited proli­feration in Panc-1 cells. Cells surviving high-dose gemcitabine treatment express increased levels of stem cell genes, show characteristics associated with epithelial-mesenchymal transition and retain their proliferative capacity.
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Copy and paste a formatted citation
Spandidos Publications style
Quint K, Tonigold M, Di Fazio P, Montalbano R, Lingelbach S, Rückert F, Alinger B, Ocker M and Neureiter D: Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition. Int J Oncol 41: 2093-2102, 2012.
APA
Quint, K., Tonigold, M., Di Fazio, P., Montalbano, R., Lingelbach, S., Rückert, F. ... Neureiter, D. (2012). Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition. International Journal of Oncology, 41, 2093-2102. https://doi.org/10.3892/ijo.2012.1648
MLA
Quint, K., Tonigold, M., Di Fazio, P., Montalbano, R., Lingelbach, S., Rückert, F., Alinger, B., Ocker, M., Neureiter, D."Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition". International Journal of Oncology 41.6 (2012): 2093-2102.
Chicago
Quint, K., Tonigold, M., Di Fazio, P., Montalbano, R., Lingelbach, S., Rückert, F., Alinger, B., Ocker, M., Neureiter, D."Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition". International Journal of Oncology 41, no. 6 (2012): 2093-2102. https://doi.org/10.3892/ijo.2012.1648
Copy and paste a formatted citation
x
Spandidos Publications style
Quint K, Tonigold M, Di Fazio P, Montalbano R, Lingelbach S, Rückert F, Alinger B, Ocker M and Neureiter D: Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition. Int J Oncol 41: 2093-2102, 2012.
APA
Quint, K., Tonigold, M., Di Fazio, P., Montalbano, R., Lingelbach, S., Rückert, F. ... Neureiter, D. (2012). Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition. International Journal of Oncology, 41, 2093-2102. https://doi.org/10.3892/ijo.2012.1648
MLA
Quint, K., Tonigold, M., Di Fazio, P., Montalbano, R., Lingelbach, S., Rückert, F., Alinger, B., Ocker, M., Neureiter, D."Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition". International Journal of Oncology 41.6 (2012): 2093-2102.
Chicago
Quint, K., Tonigold, M., Di Fazio, P., Montalbano, R., Lingelbach, S., Rückert, F., Alinger, B., Ocker, M., Neureiter, D."Pancreatic cancer cells surviving gemcitabine treatment express markers of stem cell differentiation and epithelial-mesenchymal transition". International Journal of Oncology 41, no. 6 (2012): 2093-2102. https://doi.org/10.3892/ijo.2012.1648
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