Different Capabilities of Morphological Pattern Formation and Its Association with the Expression of Differentiation Markers in a Xenograft Model of Human Pancreatic Cancer Cell Lines

Vol. 5, No. 4-5, 2005

Free Abstract Article (References) Article (PDF 594 KB)

Original Paper

Different Capabilities of Morphological Pattern Formation and Its Association with the Expression of Differentiation Markers in a Xenograft Model of Human Pancreatic Cancer Cell Lines
Daniel Neureiter^a, Steffen Zopf^b, Arno Dimmler^a, Sebastian Stintzing^b, Eckhart G. Hahn^b, Thomas Kirchner^a, Christoph Herold^b, Matthias Ocker^b

Departments of
^aPathology and
^bMedicine I, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany and
^cInstitute of Pathology, Landeskliniken Salzburg, Salzburg, Austria

Address of Corresponding Author

Pancreatology 2005;5:387-397 (DOI: 10.1159/000086539)

Key Words

Pancreatic carcinoma cell lines
Xenografts
Transitions states
Transdifferentiation
Dedifferentiation

Abstract

Aims: New concepts of tumorigenesis favor an unregulated process recapitulating different stages of embryogenic development with dysregulation of transition states. The aim of our study was to investigate the possibility of differentiation pathways of human pancreatic cancer cell lines in vivo. Material and Methods: Different human pancreatic cancer cell lines (YAPC, DAN-G, CAPAN-1, PANC-1 and MIA PaCa-2) were implanted subcutaneously (3 × 10⁶ cells) for 28 days in nude mice. Xenotransplants were characterized with histochemistry (HE, PAS), immunohistochemistry (cytokeratin (CK)7, CK8, CK18, CK19, CK20, vimentin, chromogranin A (Chr-A), alpha ₁-antichymotrypsin ( alpha ₁-chym), beta -catenin, laminin-5, pancreatic and duodenal homeobox gene 1 (pdx-1), sonic hedgehog protein (shh), Patched (ptc)), Western blotting and real-time PCR (CK7, CK8, CK20, Chr-A, pdx-1, shh, ptc). Results: Depending on three major morphologic phenotypes of tumor cell xenotransplants (ductal (YAPC), ductal/solid (DAN-G, CAPAN-1), solid (PANC-1, MIA PaCa-2)), a decrease of CK7/CK19 was found, accompanied by an increase of CK8/18 and vimentin. Predominantly the CK7-positive ductal phenotype (YAPC and DAN-G) was associated with pdx-1 expression, whereas the CK8-positive solid phenotype was associated with shh/ptc expression on protein and mRNA level. Additionally, CK-20 expression was mainly linked to the ductal phenotype, co-localized with nuclear beta -catenin. The endocrine-exocrine transdifferentiation, as assessed by Chr-A and alpha ₁-chym, was on a constant low to moderate level in all xenotransplants. Finally, an intensive epithelial-mesenchymal interaction was observed by overexpression of laminin-5 at the invasion front. Conclusion: The observed patterns of morphology and molecular differentiation in human pancreatic cancer xenografts indicate that these cancer cell lines have different capa bilities of pattern formation in vivoassociated with molecular differentiation markers, especially of embryonic pancreatic development.

Author Contacts

D. Neureiter, MD
Institute of Pathology, Salzburger Landeskliniken
Paracelsus Private Medical University, Müllnerstrasse 48, A-5020 Salzburg (Austria)
Tel. +43 662 4482 4737, Fax +43 662 4482 882
E-Mail d.neureiter@salk.at

Article Information

D.N., S.Z. and A.D. contributed equally to this work.

Received: September 20, 2004
Accepted after revision: March 28, 2005
Published online: June 23, 2005
Number of Print Pages : 11
Number of Figures : 3, Number of Tables : 3, Number of References : 43

Medline Abstract (ID 15980667)

Download Citation

Cited In

For non-native English speakers and international authors who would like assistance with their writing before submission, we suggest American Journal Experts for their scientific editing service.