Establishment and characterization of 4 new human pancreatic cancer cell lines: evidences of different tumor phenotypes.
OBJECTIVE
Pancreatic cancer still remains a challenge for its biological complexity and lack of effective therapeutic strategies. Establishing new pancreatic cancer cell lines is therefore of paramount importance to clarify its biology.


METHODS
We established and characterized 4 new pancreatic cancer cell lines (PP78, PP109, PP117, and PP161) according to their genetic (K-Ras, TP53, CDKN2A, and MADH4; DNA fingerprinting; karyotype), cytostructural (cytokeratins 7, 8, 18, and 19 vimentin, and ezrin), and functional profiles (doubling time; migration assay).


RESULTS
K-Ras, TP53, and CDKN2A gene alterations were detected in all 4 of them. Each cell line had a unique DNA profile revealed by DNA fingerprinting. A complex karyotype with numerous structural and numeric chromosomal abnormalities was present in each cell line. All 4 cell lines showed positivity for cytokeratins 7, 8, and 18. All but PP78 expressed cytokeratin 19, whereas vimentin was expressed only in PP117 and PP78 cells. A different ezrin cellular distribution was noticed in PP78 and PP117, being mostly located at membrane ruffles. This peculiar distribution was associated with the strongest migratory capability.


CONCLUSIONS
Our results seem to confirm the pancreatic ductal adenocarcinoma heterogeneity; in fact, the same genetic abnormalities (K-Ras, TP53, and CDKN2A) may have different effects on tumor biology depending on cellular differentiation.
Chifenti
Barbara
B
Division of Surgical, Regional Referral Center for Pancreatic Diseases Treatment, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy. b.chifenti@dottoratooncologia.pisa.it
Morelli
Mariangela
M
Zavaglia
Michele
M
Coviello
Domenico A
DA
Guerneri
Silvana
S
Santucci
Annalisa
A
Paffetti
Alessandro
A
Masetti
Massimo
M
Locci
Maria Teresa
MT
Bertacca
Gloria
G
Capodanno
Alessandra
A
Collecchi
Paola
P
Campani
Daniela
D
Mosca
Franco
F
Bevilacqua
Generoso
G
Cavazzana
Andrea O
AO
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016172:DNA Fingerprinting; D005260:Female; D019942:Genes, p16; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D051901:Smad4 Protein / Q000235:genetics; D014746:Vimentin / Q000032:analysis
C497796:SMAD4 protein, human; D051901:Smad4 Protein; D014746:Vimentin; D007633:Keratins