Cold Atmospheric Plasma Does Not Affect Stellate Cells Phenotype in Pancreatic Cancer Tissue in Ovo.

Angela Privat-Maldonado,Ruben Verloy,Edgar Cardenas Delahoz,Evelien Smits,Annemie Bogaerts,Abraham Lin,Steve Vanlanduit

doi:10.3390/ijms23041954

Angela Privat-Maldonado, Ruben Verloy + Show 5 more

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https://doi.org/10.3390/ijms23041954

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a challenging neoplastic disease, mainly due to the development of resistance to radio- and chemotherapy. Cold atmospheric plasma (CAP) is an alternative technology that can eliminate cancer cells through oxidative damage, as shown in vitro, in ovo, and in vivo. However, how CAP affects the pancreatic stellate cells (PSCs), key players in the invasion and metastasis of PDAC, is poorly understood. This study aims to determine the effect of an anti-PDAC CAP treatment on PSCs tissue developed in ovo using mono- and co-cultures of RLT-PSC (PSCs) and Mia PaCa-2 cells (PDAC). We measured tissue reduction upon CAP treatment and mRNA expression of PSC activation markers and extracellular matrix (ECM) remodelling factors via qRT-PCR. Protein expression of selected markers was confirmed via immunohistochemistry. CAP inhibited growth in Mia PaCa-2 and co-cultured tissue, but its effectiveness was reduced in the latter, which correlates with reduced ki67 levels. CAP did not alter the mRNA expression of PSC activation and ECM remodelling markers. No changes in MMP2 and MMP9 expression were observed in RLT-PSCs, but small changes were observed in Mia PaCa-2 cells. Our findings support the ability of CAP to eliminate PDAC cells, without altering the PSCs.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent oncologic disease of the pancreas, responsible for approximately 85% of all pancreatic malignancies [1]
The crosstalk between pancreatic stellate cells (PSCs) and PDAC cells creates a specific tumour microenvironment (TME) that accelerates the proliferation of PDAC cells, inhibits their apoptosis and can induce their epithelial-mesenchymal transition (EMT), making them more migratory [7]
We have focused this study on the effect of Cold atmospheric plasma (CAP) in PSCs because the stroma regulates the molecular interactions with the extracellular matrix (ECM), is responsible for the remodelling of the TME in PDAC, and facilitates the invasion and metastasis of cancer cells [46]

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent oncologic disease of the pancreas, responsible for approximately 85% of all pancreatic malignancies [1]. A limiting factor of the main current therapies is that most of them target only the cancer cells, without considering the key role played by stromal cells. PDAC is characterized by its fast progression and desmoplastic reaction, orchestrated by the interplay between cancer cells and the surrounding tumour stromal cells [3]. The thick desmoplastic stroma accounts for up to 90% of the tumour volume and contains endothelial cells, immune cells, collapsed blood vessels, as well as pancreatic stellate cells (PSCs), which deposit large amounts of extracellular matrix components [4]. PSCs make up 4–7% of pancreatic cells in normal tissue and are present in a quiescent state, where they regulate the production and turnover of extracellular matrix (ECM) components [6]. The crosstalk between PSCs and PDAC cells creates a specific tumour microenvironment (TME) that accelerates the proliferation of PDAC cells, inhibits their apoptosis and can induce their epithelial-mesenchymal transition (EMT), making them more migratory [7]

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