MIA PaCa-2 and PANC-1 – pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors

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.

PGRMC1 phosphorylation and cell plasticity 1: glycolysis, mitochondria, tumor growth

“…Prominent visible features include small white lipid droplets and cholesterol-rich mitochondria (Cahill and Medlock, 2017), as well as nuclear membrane and nucleoli. The previously described MIA PaCa-2 cell bleb-like protrusions (Gradiz et al, 2016) are apparent as highly dynamic rearrangements of the cytoplasmic membrane, which may contribute to intercellular communication.…”

“…MP cells exist in culture as a mixed adherent population of elongated "fibroblast-shaped" morphology, a minority population of rounded morphology with bleb-like protrusions, and some multicellular clumps, as well as some rounded suspension cells. They have undergone epithelial-mesenchymal transition (Gradiz et al, 2016), and can further undergo mesenchymal-amoeboid transition (MAT), which requires Rho Kinase-(ROCK)-dependent morphological change from "elongated" mesenchymal cells to rounded amoeboid cells (Fujita et al, 2011).…”

Enhancing Drug Efficacy and Therapeutic Index through Cheminformatics-Based Selection of Small Molecule Binary Weapons That Improve Transporter-Mediated Targeting: A Cytotoxicity System Based on Gemcitabine

“…Panc1 cells are a pancreatic cancer cell line (e.g., Gradiz et al, 2016). Figure 1 shows four separate experiments in which the effect of the pools of the Maybridge fragments (6 at a time) on the viability of cells was assessed in the presence and absence of 20 nM gemcitabine, pointing up three pools containing “hits” (which occurred in at least 3 experiments; there are a total of 336 experiments here).…”

Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer

“…, 2009; Shahbaz et al. , 2015; Gradiz et al. , 2016), SSTR2 has been observed at low but detectable levels.…”

“…, 2000; Li et al. , 2004b; Gradiz et al. , 2016), SSTR2, CXCR4, and MOR were expressed at higher levels in a pancreatic cancer environment than in normal pancreatic cells.…”