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Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening

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Abstract

Background

Efforts to identify novel therapeutic options for human pancreatic ductal adenocarcinoma (PDAC) have failed to result in a clear improvement in patient survival to date. Pancreatic cancer requires efficient therapies that must be designed and assayed in preclinical models with improved predictor ability. Among the available preclinical models, the orthotopic approach fits with this expectation, but its use is still occasional.

Methods

An in vivo platform of 11 orthotopic tumor xenografts has been generated by direct implantation of fresh surgical material. In addition, a frozen tumorgraft bank has been created, ensuring future model recovery and tumor tissue availability.

Results

Tissue microarray studies allow showing a high degree of original histology preservation and maintenance of protein expression patterns through passages. The models display stable growth kinetics and characteristic metastatic behavior. Moreover, the molecular diversity may facilitate the identification of tumor subtypes and comparison of drug responses that complement or confirm information obtained with other preclinical models.

Conclusions

This panel represents a useful preclinical tool for testing new agents and treatment protocols and for further exploration of the biological basis of drug responses.

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Acknowledgments

This research was supported by Ministerio de Ciencia e Innovación, Grant BIO2005-08682-C03-03 and BIO2008-04692-C03-03 and Ministerio de Sanidad y Consumo, Grant 03/156. AVP has been FI fellow recipient.

We are very grateful to Raquel Longarón, Eva Fernández, and Ingrid Victoria for technical work in characterization of gene status, tissue microarrays and histochemistry/immunohistochemistry, respectively.

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Authors and Affiliations

  1. Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina, Universitat de Barcelona, Diagonal 645, 08028, Barcelona, Spain

    Sandra Pérez-Torras, Anna Vidal-Pla, Neus Carbó & Adela Mazo

  2. Serveis de Patologia, Hospital Clínic de Barcelona (HCB), Barcelona, Spain

    Rosa Miquel

  3. Oncologia, Hospital Clínic de Barcelona (HCB), Barcelona, Spain

    Vanessa Almendro, Joan Maurel & Pere Gascón

  4. Cirurgia, Hospital Clínic de Barcelona (HCB), Barcelona, Spain

    Laureano Fernández-Cruz

  5. Gastroenterologia, Hospital Clínic de Barcelona (HCB), Barcelona, Spain

    Salvador Navarro

  6. Institut d’Investigació Biomèdica August Pí i Sunyer (IDIBAPS), Barcelona, Spain

    Salvador Navarro, Joan Maurel & Pere Gascón

  7. Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain

    Sandra Pérez-Torras, Salvador Navarro & Joan Maurel

  8. Red Temática de Investigación Cooperativa en Cáncer (RTICC), Barcelona, Spain

    Pere Gascón

  9. Departament de Bioquímica i Biología Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028, Barcelona, Spain

    Adela Mazo

Authors
  1. Sandra Pérez-Torras
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  2. Anna Vidal-Pla
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Correspondence to Adela Mazo.

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Supplemental 1

Macroscopic picture representative of a pancreatic resection and tissue sampling. Macroscopic features of a ductal pancreatic adenocarcinoma (CP2). A cross section of the pancreatic head show a 2.5 cm tumor which can be identified as a solid nodular area. The limit of the tumor is marked with a dotted line. A fresh tumor tissue sample was obtained (black arrowhead) to be implanted in the mice and to be stored frozen. Normal pancreatic tissue can be observed at the left side of the surgical specimen, nearby the resection margin. The white arrowhead shows the place where the normal tissue sample was taken. (DOC 745 kb)

Supplemental 2

Hematoxylin-eosin staining of primary human tumors and their corresponding xenografted tumors (2nd or 3th generations) (PPT 44246 kb)

Supplemental 3

Microphotography of tumorgrafts showing transition zones between tumor and normal pancreas. Acini representative of normal pancreas (→). Tumor areas (*) (PPT 997 kb)

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Pérez-Torras, S., Vidal-Pla, A., Miquel, R. et al. Characterization of human pancreatic orthotopic tumor xenografts suitable for drug screening. Cell Oncol. 34, 511–521 (2011). https://doi.org/10.1007/s13402-011-0049-1

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