Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2023

Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro

Résumé

Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by an acidic microenvironment, which contributes to therapeutic failure. So far there is a lack of knowledge with respect to the role of the acidic microenvironment in the invasive process. This work aimed to study the phenotypic and genetic response of PDAC cells to acidic stress along the different stages of selection. To this end, we subjected the cells to short- and long-term acidic pressure and recovery to pHe 7.4. This treatment aimed at mimicking PDAC edges and consequent cancer cell escape from the tumor. The impact of acidosis was assessed for cell morphology, proliferation, adhesion, migration, invasion, and epithelial–mesenchymal transition (EMT) via functional in vitro assays and RNA sequencing. Our results indicate that short acidic treatment limits growth, adhesion, invasion, and viability of PDAC cells. As the acid treatment progresses, it selects cancer cells with enhanced migration and invasion abilities induced by EMT, potentiating their metastatic potential when re-exposed to pHe 7.4. The RNA-seq analysis of PANC-1 cells exposed to short-term acidosis and pHe-selected recovered to pHe 7.4 revealed distinct transcriptome rewiring. We describe an enrichment of genes relevant to proliferation, migration, EMT, and invasion in acid-selected cells. Our work clearly demonstrates that upon acidosis stress, PDAC cells acquire more invasive cell phenotypes by promoting EMT and thus paving the way for more aggressive cell phenotypes.
Fichier principal
Vignette du fichier
cancers-15-02572-v3.pdf (6.51 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-04277332 , version 1 (11-04-2024)

Identifiants

Citer

Madelaine Magalì Audero, Tiago Miguel Amaral Carvalho, Federico Alessandro Ruffinatti, Thorsten Loeck, Maya Yassine, et al.. Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro. Cancers, 2023, 15 (9), pp.2572. ⟨10.3390/cancers15092572⟩. ⟨hal-04277332⟩
13 Consultations
1 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More