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Orthotopic transplantation models of pancreatic adenocarcinoma derived from cell lines and primary tumors and displaying varying metastatic activity.
Pancreas 2004; 29(3):193-203P

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.

Authors+Show Affiliations

Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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://dx.doi.org/10.1097/00006676-200410000-00004 DB - PRIME DP - Unbound Medicine ER -