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Orthotopic transplantation models of pancreatic adenocarcinoma derived from cell lines and primary tumors and displaying varying metastatic activity.

Abstract

OBJECTIVE

To establish a series of clinically relevant orthotopic transplantation models of human pancreatic adenocarcinoma from both cell lines and primary tumors under uniform experimental conditions.

METHODS

Ten pancreatic cancer cell lines and 12 primary tumors were orthotopically transplanted in SCID mice. The cell lines and xenografts were characterized for K-ras, BRAF, p53, p16, and DPC4 aberrations employing direct sequencing, immunohistochemistry, and Western blotting.

RESULTS

All xenografts showed high intrapancreatic tumorigenicity and extensive local tumor growth, and each showed a unique behavioral and genetic profile. Tumor characteristics were retained during serial passaging. The cell line-derived xenografts represented the entire expected range of histologic differentiation. Although the overall metastatic rate was moderate to high, the metastatic pattern varied; 4 cell lines showed a high metastatic rate to the liver. The primary tumor-derived xenografts retained their similarity to the corresponding original donor tumors with regard to histologic presentation and biologic behavior. K-ras, p53, p16, and DPC4 aberrations were revealed in 80%, 70%, 50%, and 40% of cell lines and 100%, 33%, 75%, and 58% of primary tumor derived xenografts, respectively. No BRAF mutations were present. The metastatic behavior of the xenografts was significantly associated with the degree of histologic differentiation, number of genes altered, and p53 status.

CONCLUSIONS

The new models reflected the wide range of patho-biological features and genetic alterations that characterize human pancreatic cancer and may be used collectively or selectively as a markedly improved in vivo tool for preclinical and molecular studies of pancreatic cancer.

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  • Authors+Show Affiliations

    ,

    Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.

    , , , ,

    Source

    Pancreas 29:3 2004 Oct pg 193-203

    MeSH

    Adenocarcinoma
    Animals
    Blotting, Western
    Cell Differentiation
    Cell Line, Tumor
    Cyclin-Dependent Kinase Inhibitor p16
    DNA Mutational Analysis
    DNA, Neoplasm
    DNA-Binding Proteins
    Gene Deletion
    Genes, p16
    Genes, p53
    Genes, ras
    Humans
    Liver Neoplasms
    Lung Neoplasms
    Lymphatic Metastasis
    Male
    Mice
    Mice, SCID
    Mutation, Missense
    Neoplasm Proteins
    Neoplasm Transplantation
    Pancreas
    Pancreatic Neoplasms
    Peritoneal Neoplasms
    Polymerase Chain Reaction
    Proto-Oncogene Proteins B-raf
    Proto-Oncogene Proteins p21(ras)
    Smad4 Protein
    Specific Pathogen-Free Organisms
    Trans-Activators
    Transplantation, Heterologous
    Tumor Suppressor Protein p53

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15367885

    Citation

    Loukopoulos, Panayiotis, et al. "Orthotopic Transplantation Models of Pancreatic Adenocarcinoma Derived From Cell Lines and Primary Tumors and Displaying Varying Metastatic Activity." Pancreas, vol. 29, no. 3, 2004, pp. 193-203.
    Loukopoulos P, Kanetaka K, Takamura M, et al. Orthotopic transplantation models of pancreatic adenocarcinoma derived from cell lines and primary tumors and displaying varying metastatic activity. Pancreas. 2004;29(3):193-203.
    Loukopoulos, P., Kanetaka, K., Takamura, M., Shibata, T., Sakamoto, M., & Hirohashi, S. (2004). Orthotopic transplantation models of pancreatic adenocarcinoma derived from cell lines and primary tumors and displaying varying metastatic activity. Pancreas, 29(3), pp. 193-203.
    Loukopoulos P, et al. Orthotopic Transplantation Models of Pancreatic Adenocarcinoma Derived From Cell Lines and Primary Tumors and Displaying Varying Metastatic Activity. Pancreas. 2004;29(3):193-203. PubMed PMID: 15367885.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Orthotopic transplantation models of pancreatic adenocarcinoma derived from cell lines and primary tumors and displaying varying metastatic activity. AU - Loukopoulos,Panayiotis, AU - Kanetaka,Kengo, AU - Takamura,Masaaki, AU - Shibata,Tatsuhiro, AU - Sakamoto,Michiie, AU - Hirohashi,Setsuo, PY - 2004/9/16/pubmed PY - 2005/5/17/medline PY - 2004/9/16/entrez SP - 193 EP - 203 JF - Pancreas JO - Pancreas VL - 29 IS - 3 N2 - OBJECTIVE: To establish a series of clinically relevant orthotopic transplantation models of human pancreatic adenocarcinoma from both cell lines and primary tumors under uniform experimental conditions. METHODS: Ten pancreatic cancer cell lines and 12 primary tumors were orthotopically transplanted in SCID mice. The cell lines and xenografts were characterized for K-ras, BRAF, p53, p16, and DPC4 aberrations employing direct sequencing, immunohistochemistry, and Western blotting. RESULTS: All xenografts showed high intrapancreatic tumorigenicity and extensive local tumor growth, and each showed a unique behavioral and genetic profile. Tumor characteristics were retained during serial passaging. The cell line-derived xenografts represented the entire expected range of histologic differentiation. Although the overall metastatic rate was moderate to high, the metastatic pattern varied; 4 cell lines showed a high metastatic rate to the liver. The primary tumor-derived xenografts retained their similarity to the corresponding original donor tumors with regard to histologic presentation and biologic behavior. K-ras, p53, p16, and DPC4 aberrations were revealed in 80%, 70%, 50%, and 40% of cell lines and 100%, 33%, 75%, and 58% of primary tumor derived xenografts, respectively. No BRAF mutations were present. The metastatic behavior of the xenografts was significantly associated with the degree of histologic differentiation, number of genes altered, and p53 status. CONCLUSIONS: The new models reflected the wide range of patho-biological features and genetic alterations that characterize human pancreatic cancer and may be used collectively or selectively as a markedly improved in vivo tool for preclinical and molecular studies of pancreatic cancer. SN - 1536-4828 UR - https://www.unboundmedicine.com/medline/citation/15367885/Orthotopic_transplantation_models_of_pancreatic_adenocarcinoma_derived_from_cell_lines_and_primary_tumors_and_displaying_varying_metastatic_activity_ L2 - http://Insights.ovid.com/pubmed?pmid=15367885 DB - PRIME DP - Unbound Medicine ER -