Selenite modulates phenotype-dependent epithelial-mesenchymal plasticity in pancreatic ductal adenocarcinoma: integrated in vitro analyses and patient-derived ex vivo tissue-slice cultures.

Authors

Ozan Aricak, Wenyang Shi, Carlos Fernández Moro, Mehran Ghaderi, Joakim Dillner, Jonas Fuxe, Mikael Björnstedt, Tímea Szekerczés

Published in

Journal of experimental & clinical cancer research : CR. Volume 45. Issue 1. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by profound therapy resistance, desmoplasia, and phenotypic plasticity. While sodium selenite is a redox-active compound with reported tumor-selective cytotoxicity, its impact on epithelial-mesenchymal transition (EMT) states in PDAC remains insufficiently defined. We investigated whether selenite modulates EMT-associated phenotypes in a dose- and context-dependent manner using complementary in vitro and patient-derived ex vivo models and linked marker shifts to histological tumor regression in PDAC tissue slices.
Three PDAC cell lines spanning distinct baseline EMT states (PANC-1, HPAF-II, Capan-2) were profiled by quantitative immunofluorescence for a predefined epithelial (EpCAM, cytokeratin, E-cadherin) and mesenchymal-associated (AHNAK2, ITGAV, vimentin) protein panel, with or without TGF-β pretreatment. Ex vivo tissue slices from treatment-naïve, non-metastatic PDAC resections (n = 10) were cultured in a within-patient paired design (0 h, 24 h, 48 h controls; 5 or 15 µM selenite during the second 24 h). Histological tumor regression was scored by a blinded pancreatic pathologist (Evans; CAP), compartment-resolved marker expression was quantified by multiplex immunofluorescence, and paired RNA sequencing was performed in a subset of donors (n = 4).
In vitro, responses were phenotype-contingent: the epithelial-biased HPAF-II and Capan-2 lines showed partial epithelial reinforcement and a consistent reduction of mesenchymal markers (particularly ITGAV, vimentin), whereas the mesenchymal-biased PANC-1 exhibited limited modulation. TGF-β pretreatment attenuated epithelial-promoting effects while suppression of mesenchymal markers was retained in a cell line-dependent manner. In ex vivo slices, selenite induced a dose-dependent improvement in histological tumor regression and increased the tumor-compartment epithelial-mesenchymal ratio at 15 µM, driven mainly by epithelial-marker upregulation, while mesenchymal markers showed no uniform suppression. At 15 µM, transcriptomics revealed a compact treatment response characterized by downregulation of basement-membrane/ECM modules without broad reversal across EMT gene sets; EMT scoring indicated heterogeneous shifts at 5 µM and a more consistent epithelial-leaning shift at 15 µM in most donors.
Selenite was associated with reinforcement of epithelial features mainly in malignant PDAC compartments in a baseline-state-, dose-, and context-dependent manner, with higher-dose phenotypic shifts occurring alongside stronger histological tumor response in clinically proximal models.
Not applicable.

PMID:
42443972
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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