Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2021; 27(15): 1616-1629
Published online Apr 21, 2021. doi: 10.3748/wjg.v27.i15.1616
Effects of CXCL12 isoforms in a pancreatic pre-tumour cellular model: Microarray analysis
Monia Cecati, Matteo Giulietti, Alessandra Righetti, Berina Sabanovic, Francesco Piva
Monia Cecati, Matteo Giulietti, Alessandra Righetti, Berina Sabanovic, Francesco Piva, Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Ancona 60126, Italy
Author contributions: Piva F designed and coordinated the study; Cecati M and Righetti A performed the experiments, acquired and analyzed data; Giulietti M and Sabanovic B analyzed and interpreted the data; Giulietti M, Sabanovic B and Cecati M wrote the manuscript; all authors approved the final version of the article.
Supported by Fondazione Cariverona, No. 2017.0570 (to Piva F).
Institutional review board statement: The authors declare that the requirement of the Institutional Review Board Approval Form or Document is not applicable, since the experiments did not involve humans.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Data sharing statement: Datasets available from the corresponding author at m.giulietti@univpm.it.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Matteo Giulietti, PhD, Academic Research, Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Via Brecce Bianche, Ancona 60126, Italy. m.giulietti@univpm.it
Received: January 28, 2021
Peer-review started: January 28, 2021
First decision: February 24, 2021
Revised: March 5, 2021
Accepted: March 29, 2021
Article in press: March 29, 2021
Published online: April 21, 2021
ARTICLE HIGHLIGHTS
Research background

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer type, since it is usually diagnosed late, it has a very poor prognosis and strong chemoresistance. In the tumour microenvironment, cancer cells and other cell types co-exist and communicate by exchanging several molecules, including the chemokine CXCL12.

Research motivation

CXCL12 pre-mRNA can be alternatively spliced into different isoforms (α, β, γ, δ, ε, θ). However, their specific roles in PDAC have not yet been fully described.

Research objectives

Here, we aim to evaluate the specific roles of the main CXCL12 isoforms (α, β, and γ) in PDAC onset.

Research methods

We administered α, β, and γ CXCL12 isoforms to a pre-tumour model of PDAC, i.e., the hTERT-HPNE E6/E7/KRasG12D cells. Then, we performed microarray analysis and Real-Time polymerase chain reaction validation in order to evaluate the global gene expression alterations. We also carried out wound healing assays in order to evaluate the effect of α, β, and γ CXCL12 isoforms on the cell migration ability.

Research results

The transcriptomic analyses showed that the expression of only few genes was affected by the treatment with the three isoforms. In particular, α and β isoforms affect different genes, whereas γ isoform altered the expression of genes already affected by the other isoforms. Since many genes affected by all isoforms are involved in cell migration and cytoskeleton remodelling, we performed cell migration assays, which confirmed the role of CXCL12 in migration, mainly caused by the γ isoform.

Research conclusions

Our results suggest that α, β and γ CXCL12 isoforms can trigger different responses in a pancreatic pre-tumour model. The γ isoform induced the highest level of cell migration.

Research perspectives

Although our data shed light on the molecular basis of PDAC onset and progression, further studies are necessary for a deeper characterization of CXCL12 isoforms.