当前位置： SCI文献检索 > BMC CANCER期刊下所有文献 > The A818-6 system as an in-vitro model for studying the role of the transportome in pancreatic cancer.

The A818-6 system as an in-vitro model for studying the role of the transportome in pancreatic cancer.

Abstract：

BACKGROUND:The human pancreatic cancer cell line A818-6 can be grown in vitro either as a highly malignant, undifferentiated monolayer (ML) or as three-dimensional (3D) single layer hollow spheres (HS) simulating a benign, highly differentiated, duct-like pancreatic epithelial structure. This characteristic allowing A818-6 cells to switch from one phenotype to another makes these cells a unique system to characterize the cellular and molecular modifications during differentiation on one hand and malignant transformation on the other hand. Ion channels and transport proteins (transportome) have been implicated in malignant transformation. Therefore, the current study aimed to analyse the transportome gene expression profile in the A818-6 cells growing as a monolayer or as hollow spheres. METHODS & RESULTS:The study identified the differentially expressed transportome genes in both cellular states of A818-6 using Agilent and Nanostring arrays and some targets were validated via immunoblotting. Additionally, these results were compared to a tissue Affymetrix microarray analysis of pancreatic adenocarcinoma patients' tissues. The overall transcriptional profile of the ML and HS cells confirmed the formerly described mesenchymal features of ML and epithelial nature of HS which was further verified via high expression of E-cadherin and low expression of vimentin found in HS in comparison to ML. Among the predicted features between HS and ML was the involvement of miRNA-9 in this switch. Importantly, the bioinformatics analysis also revealed substantial number (n = 126) of altered transportome genes. Interestingly, three genes upregulated in PDAC tissue samples (GJB2, GJB5 and SLC38A6) were found to be also upregulated in ML and 3 down-regulated transportome genes (KCNQ1, TRPV6 and SLC4A) were also reduced in ML. CONCLUSION:This reversible HS/ML in vitro system might help in understanding the pathophysiological impact of the transportome in the dedifferentiation process in pancreatic carcinogenesis. Furthermore, the HS/ML model represents a novel system for studying the role of the transportome during the switch from a more benign, differentiated (HS) to a highly malignant, undifferentiated (ML) phenotype.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Tawfik D,Zaccagnino A,Bernt A,Szczepanowski M,Klapper W,Schwab A,Kalthoff H,Trauzold A

doi

10.1186/s12885-020-06773-w

subject

Has Abstract

pub_date

2020-03-30 00:00:00

pages

264

issue

issn

1471-2407

pii

10.1186/s12885-020-06773-w

journal_volume

pub_type

杂志文章

在线工具

The A818-6 system as an in-vitro model for studying the role of the transportome in pancreatic cancer.