Cell cannibalism, a cell-death process driven by the Transforming Growth Factor-M-NM-2 and the Nuclear Protein 1, opposes to metastasis in pancreatic cancer

ABSTRACT: Pancreatic adenocarcinoma (PDAC) is an extremely deadly disease for which all treatments available have failed to improve life expectancy significantly. This may be explained by the high metastatic potential of PDAC cells, which results from their physiological dedifferentiation towards a mesenchymal phenotype. Some PDAC present cell-in-cell structures but their origin and significance is currently unknown. We show here that cell-incells form after cell cannibalism. We found PDAC patients whose tumors display cell cannibalism develop less metastasis than those without. In vitro, cell cannibalism was enhanced by the TGFM-NM-2 and repressed by the Nuclear protein (Nupr)1, and was coupled to a defective epithelial-to-mesenchymal transition of PDAC cells. Cannibalism ends with death of PDAC cells, consistent with a metastasis suppressor role for this phenomenon. Hence, our data indicates a protective role for cell cannibalism in PDAC and identifies Nupr1 and TGFM-NM-2 as molecular regulators of this process. Cell culture and culture reagents. Panc-1 cells were cultured in Glutamax-containing DMEM(Invitrogen) and BxPC3 in RPMI (Invitrogen), both supplemented with 10% FBS (PAA Laboratories). All cells were maintained at 37M-BM-0C, 5% CO2, H2O saturated. TGFM-NM-21 (Peprotech) was used at 10 ng/ml .siRNA-mediated gene silencing. Panc-1 cells were seeded in 6-wells plates to reach 30% to 50% confluence. Twenty-four hours later, a mix containing 2.2 pmoles of siRNA and 8 M-NM-

ORGANISM(S): Homo sapiens

SUBMITTER: Ezequiel Calvo 

PROVIDER: E-GEOD-38772 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress