Establishment and characterization of a highly tumourigenic and cancer stem cell enriched pancreatic cancer cell line as a well defined model system

PLoS One. 2012;7(11):e48503. doi: 10.1371/journal.pone.0048503. Epub 2012 Nov 12.

Abstract

Standard cancer cell lines do not model the intratumoural heterogeneity situation sufficiently. Clonal selection leads to a homogeneous population of cells by genetic drift. Heterogeneity of tumour cells, however, is particularly critical for therapeutically relevant studies, since it is a prerequisite for acquiring drug resistance and reoccurrence of tumours. Here, we report the isolation of a highly tumourigenic primary pancreatic cancer cell line, called JoPaca-1 and its detailed characterization at multiple levels. Implantation of as few as 100 JoPaca-1 cells into immunodeficient mice gave rise to tumours that were histologically very similar to the primary tumour. The high heterogeneity of JoPaca-1 was reflected by diverse cell morphology and a substantial number of chromosomal aberrations. Comparative whole-genome sequencing of JoPaca-1 and BxPC-3 revealed mutations in genes frequently altered in pancreatic cancer. Exceptionally high expression of cancer stem cell markers and a high clonogenic potential in vitro and in vivo was observed. All of these attributes make this cell line an extremely valuable model to study the biology of and pharmaceutical effects on pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Aldehyde Dehydrogenase 1 Family
  • Alleles
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antimetabolites, Antineoplastic / pharmacology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic* / genetics
  • Cell Transformation, Neoplastic* / pathology
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Disease Models, Animal
  • Drug Resistance, Neoplasm / genetics
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Genomic Instability
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Keratins / genetics
  • Keratins / metabolism
  • Male
  • Mice
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Peptides / genetics
  • Peptides / metabolism
  • Polyploidy
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism
  • Transplantation, Heterologous
  • Tumor Microenvironment

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • Glycoproteins
  • Isoenzymes
  • Peptides
  • Deoxycytidine
  • Keratins
  • gemcitabine
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • ALDH1A1 protein, mouse
  • Retinal Dehydrogenase
  • mesothelin

Grant support

The work was financially supported by the German Ministry of Education and Research (BMBF) as part of the NGFN PaCaNet consortium (BMBF-01GS08117). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.