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Absence of calretinin protein expression in malignant mesotheliomas from asbestos-exposed NF2 mice and mouse mesothelioma cell lines from various mouse strains


Blum, Walter; Henzi, Thomas; Châtel-Soulet, Hugues-Etienne; Pecze, Laszlo; Rodriguez, Janine Wörthmüller; Vrugt, Bart; Schwaller, Beat (2018). Absence of calretinin protein expression in malignant mesotheliomas from asbestos-exposed NF2 mice and mouse mesothelioma cell lines from various mouse strains. Biomarker Research, 6:19.

Abstract

Background Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood-based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; ) in murine MM and reactive mesothelial cells in granuloma from asbestos-exposed NF2 mice, a line heterozygous for the tumor suppressor merlin (NF2), used as a mouse MM model. Additionally, we sought to ascertain the presence of calretinin in MM cell lines from other mouse strains. We also intended to investigate the role of calretinin in mesotheliomagenesis by comparing the survival of asbestos-exposed NF2 and NF2CR mice. Methods NF2 and NF2CR mice, both lines on a C57Bl/6J background, were exposed to asbestos following an established protocol. Tumor histology and asbestos-induced mortality were assessed. MM and granuloma from NF2 mice were analyzed with immunohistochemical methods for calretinin expression. Levels of mRNA and calretinin expression in tumors and MM cell lines of various mouse strains were determined by RT-qPCR and Western blot analysis, respectively. Results No expression of calretinin at the protein level was detected, neither in MM from NF2 mice, NF2 MM-derived cell lines nor immortalized mesothelial cells of mouse origin. At the mRNA level we detected expression in MM cell lines from different mouse strains. Survival of NF2 and NF2CR mice exposed to asbestos showed no significant difference in a log-rank (Kaplan-Meier) comparison. Conclusions The concomitant determination of calretinin and mesothelin blood levels has been proposed for early detection of human MM. Mouse MM models based on asbestos exposure are assumed to yield helpful information on the time course of appearance of mesothelin and calretinin in the blood of asbestos-treated mice determining the earliest time point for interventions. However, the observed absence of calretinin in MM from NF2 mice and derived cell lines, as well as from MM cells from Balb/c and C3H mice likely precludes the use of calretinin as a biomarker for mouse MM. The results also indicate possible species differences with respect to an involvement of calretinin in the formation of MM.

Abstract

Background Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood-based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; ) in murine MM and reactive mesothelial cells in granuloma from asbestos-exposed NF2 mice, a line heterozygous for the tumor suppressor merlin (NF2), used as a mouse MM model. Additionally, we sought to ascertain the presence of calretinin in MM cell lines from other mouse strains. We also intended to investigate the role of calretinin in mesotheliomagenesis by comparing the survival of asbestos-exposed NF2 and NF2CR mice. Methods NF2 and NF2CR mice, both lines on a C57Bl/6J background, were exposed to asbestos following an established protocol. Tumor histology and asbestos-induced mortality were assessed. MM and granuloma from NF2 mice were analyzed with immunohistochemical methods for calretinin expression. Levels of mRNA and calretinin expression in tumors and MM cell lines of various mouse strains were determined by RT-qPCR and Western blot analysis, respectively. Results No expression of calretinin at the protein level was detected, neither in MM from NF2 mice, NF2 MM-derived cell lines nor immortalized mesothelial cells of mouse origin. At the mRNA level we detected expression in MM cell lines from different mouse strains. Survival of NF2 and NF2CR mice exposed to asbestos showed no significant difference in a log-rank (Kaplan-Meier) comparison. Conclusions The concomitant determination of calretinin and mesothelin blood levels has been proposed for early detection of human MM. Mouse MM models based on asbestos exposure are assumed to yield helpful information on the time course of appearance of mesothelin and calretinin in the blood of asbestos-treated mice determining the earliest time point for interventions. However, the observed absence of calretinin in MM from NF2 mice and derived cell lines, as well as from MM cells from Balb/c and C3H mice likely precludes the use of calretinin as a biomarker for mouse MM. The results also indicate possible species differences with respect to an involvement of calretinin in the formation of MM.

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Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Molecular Medicine
Life Sciences > Clinical Biochemistry
Health Sciences > Biochemistry (medical)
Language:English
Date:2018
Deposited On:04 Sep 2018 14:23
Last Modified:08 Apr 2020 23:54
Publisher:BioMed Central
ISSN:2050-7771
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s40364-018-0132-0
PubMed ID:29928505

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