Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration.

Details

Serval ID
serval:BIB_9058A7D59C67
Type
Article: article from journal or magazin.
Collection
Publications
Title
Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration.
Journal
Respiratory Research
Author(s)
Blum W., Pecze L., Felley-Bosco E., Schwaller B.
ISSN
1465-993X (Electronic)
ISSN-L
1465-9921
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
16
Number
1
Pages
153
Language
english
Notes
Publication types: Journal ArticlePublication Status: epublish
Abstract
BACKGROUND: The Ca(2+)-binding protein calretinin is currently used as a positive marker for identifying epithelioid malignant mesothelioma (MM) and reactive mesothelium, but calretinin's likely role in mesotheliomagenesis remains unclear. Calretinin protects immortalized mesothelial cells in vitro from asbestos-induced cytotoxicity and thus might be implicated in mesothelioma formation. To further investigate calretinin's putative role in the early steps of MM generation, primary mesothelial cells from calretinin knockout (CR-/-) and wildtype (WT) mice were compared.
METHODS: Primary mouse mesothelial cells from WT and CR-/- mice were investigated with respect to morphology, marker proteins, proliferation, cell cycle parameters and mobility in vitro. Overexpression of calretinin or a nuclear-targeted variant was achieved by a lentiviral expression system.
RESULTS: CR-/- mice have a normal mesothelium and no striking morphological abnormalities compared to WT animals were noted. Primary mouse mesothelial cells from both genotypes show a typical "cobblestone-like" morphology and express mesothelial markers including mesothelin. In cells from CR-/- mice in vitro, we observed more giant cells and a significantly decreased proliferation rate. Up-regulation of calretinin in mesothelial cells of both genotypes increases the proliferation rate and induces a cobblestone-like epithelial morphology. The length of the S/G2/M phase is unchanged, however the G1 phase is clearly prolonged in CR-/- cells. They are also much slower to close a scratch in a confluent cell layer (2D-wound assay). In addition to a change in cell morphology, an increase in proliferation and mobility is observed, if calretinin overexpression is targeted to the nucleus. Thus, both calretinin and nuclear-targeted calretinin increase mesothelial cell proliferation and consequently, speed up the scratch-closure time. The increased rate of scratch closure in WT cells is the result of two processes: an increased proliferation rate and augmented cell mobility of the border cells migrating towards the empty space.
CONCLUSIONS: We hypothesize that the differences in proliferation and mobility between WT and CR-/- mesothelial cells are the likely result from differences in their developmental trajectories. The mechanistic understanding of the function of calretinin and its putative implication in signaling pathways in normal mesothelial cells may help understanding its role during the processes that lead to mesothelioma formation and could possibly open new avenues for mesothelioma therapy, either by directly targeting calretinin expression or indirectly by targeting calretinin-mediated downstream signaling.
Pubmed
Web of science
Open Access
Yes
Create date
12/01/2016 20:03
Last modification date
20/08/2019 15:53
Usage data