Abstract
Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry, and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24−, CD44+/++, CD326−/+ and CD133/1−, while PANC-1 is CD24−/+, CD44+, CD326−/+ and CD133/1−. Both cell lines have KRAS and TP53 mutations and homozygous deletions including the first 3 exons of CDKN2A/p16INK4A, but no SMAD4/DPC4 mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies.
Highlights
CSCs may be dependent on the phenotype for epithelial-mesenchymal transition (EMT), a primordial developmental process by which adult polarized epithelial cells undergo biochemical changes and assume a mesenchymal phenotype, acquiring an increased migratory capacity, invasiveness, resistance to apoptosis and expression of extracellular matrix components[11]
Flow cytometry was used to clarify whether in morphological terms there were two cell populations in MIA Paca-2 and three in PANC-1
MIA PaCa-2 flow cytometry results (Fig. 3) demonstrated the presence of two groups of viable cells: the population of large cells and that of small cells. This result may support the possibility that a polymorphic cell line exists
Summary
CSCs may be dependent on the phenotype for epithelial-mesenchymal transition (EMT) , a primordial developmental process by which adult polarized epithelial cells undergo biochemical changes and assume a mesenchymal phenotype, acquiring an increased migratory capacity, invasiveness, resistance to apoptosis and expression of extracellular matrix components[11]. The existence of adenocarcinomas with neuroendocrine differentiation (NED) may provide the possibility of treating this subgroup of tumors with peptide receptor radionuclide therapy, alone or associated with other forms of treatment, such as chemotherapy[21]. MIA PaCa-2 with functional SSTR2 receptors[31] and PANC-1 cell lines are primary tumors currently used as in vitro models to study pancreatic ductal adenocarcinoma carcinogenesis. Their morphological and genetic characteristics are well studied. The aim of this study was to confirm and investigate MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may be relevant for their use as in vitro models in pancreatic cancer neuroendocrine chemotherapy and peptide receptor radionuclide therapy assays
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