title: Establishment and characterization of a new human pancreatic adenocarcinoma cell line with high metastatic potential to the lung.
abstract: BACKGROUND
  Pancreatic cancer is still associated with devastating prognosis. Real progress in treatment options has still not been achieved. Therefore new models are urgently needed to investigate this deadly disease. As a part of this process we have established and characterized a new human pancreatic cancer cell line.
  
  
  METHODS
  The newly established pancreatic cancer cell line PaCa 5061 was characterized for its morphology, growth rate, chromosomal analysis and mutational analysis of the K-ras, EGFR and p53 genes. Gene-amplification and RNA expression profiles were obtained using an Affymetrix microarray, and overexpression was validated by IHC analysis. Tumorigenicity and spontaneous metastasis formation of PaCa 5061 cells were analyzed in pfp-/-/rag2-/- mice. Sensitivity towards chemotherapy was analysed by MTT assay.
  
  
  RESULTS
  PaCa 5061 cells grew as an adhering monolayer with a doubling time ranging from 30 to 48 hours. M-FISH analyses showed a hypertriploid complex karyotype with multiple numerical and unbalanced structural aberrations. Numerous genes were overexpressed, some of which have previously been implicated in pancreatic adenocarcinoma (GATA6, IGFBP3, IGFBP6), while others were detected for the first time (MEMO1, RIOK3). Specifically highly overexpressed genes (fold change > 10) were identified as EGFR, MUC4, CEACAM1, CEACAM5 and CEACAM6. Subcutaneous transplantation of PaCa 5061 into pfp-/-/rag2-/- mice resulted in formation of primary tumors and spontaneous lung metastasis.
  
  
  CONCLUSIONS
  The established PaCa 5061 cell line and its injection into pfp-/-/rag2-/- mice can be used as a new model for studying various aspects of the biology of human pancreatic cancer and potential treatment approaches for the disease.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg, Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. tkalinin@uke.de
authors.forename: Tatyana
authors.initials: T
authors.lastname: Kalinina
authors.forename: Cenap
authors.initials: C
authors.lastname: Güngör
authors.forename: Sabrina
authors.initials: S
authors.lastname: Thieltges
authors.forename: Maren
authors.initials: M
authors.lastname: Möller-Krull
authors.forename: Eva Maria Murga
authors.initials: EM
authors.lastname: Penas
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
authors.forename: Thomas
authors.initials: T
authors.lastname: Streichert
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Kalinin
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Benjamin
authors.initials: B
authors.lastname: Otto
authors.forename: Judith
authors.initials: J
authors.lastname: Dierlamm
authors.forename: Heidi
authors.initials: H
authors.lastname: Schwarzenbach
authors.forename: Katharina E
authors.initials: KE
authors.lastname: Effenberger
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Emre F
authors.initials: EF
authors.lastname: Yekebas
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D048430:Cell Shape; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D052899:Pore Forming Cytotoxic Proteins / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; C499308:Rag2 protein, mouse