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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Mesothelioma | Research

Possible reversibility between epithelioid and sarcomatoid types of mesothelioma is independent of ERC/mesothelin expression

Authors: Masataka Kojima, Kazunori Kajino, Shuji Momose, Nadila Wali, May Thinzar Hlaing, Bo Han, Liang Yue, Masaaki Abe, Tomoaki Fujii, Katsuhisa Ikeda, Okio Hino

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

Mesothelioma is histologically divided into three subgroups: epithelioid, sarcomatoid, and biphasic types. The epithelioid or sarcomatoid type is morphologically defined by polygonal or spindle-like forms of cells, respectively. The biphasic type consists of both components. It is not yet understood how histological differentiation of mesothelioma is regulated. ERC/mesothelin is expressed in most cases of the epithelioid type, but not in the sarcomatoid type of mesothelioma. Consequently, its expression is well correlated to the histological subtype. We hypothesized that ERC/mesothelin expression influences the histological differentiation of mesothelioma, and tested this hypothesis.

Methods

We performed studies using the overexpression or knockdown of ERC/mesothelin in mesothelioma cells to examine its effect on cellular morphology, growth kinetics, or migration/invasion activity, in vitro. We then transplanted ERC/mesothelin-overexpressing and control cells into the intraperitoneal space of mice. We examined the effect of ERC/mesothelin overexpression on mouse survival and tumor phenotype.

Results

In vitro cell culture manipulations of ERC/mesothelin expression did not affect cellular morphology or proliferation, although its overexpression enhanced cellular adhesion and the migration/invasion activity of mesothelioma cells. The survival rate of mice following intraperitoneal transplantation of ERC/mesothelin-overexpressing mesothelioma cells was significantly lower than that of mice with control cells. The histological evaluation of the tumors, however, did not show any morphological difference between two groups, and our hypothesis was not validated. Unexpectedly, both groups (ERC/mesothelin-overexpressing and control) of mesothelioma cells that were morphologically monophasic and spindle-like in vitro differentiated into a biphasic type consisting of polygonal and spindle-like components in the transplanted tumor, irrespective of ERC/mesothelin expression.

Conclusions

These results suggested that the histological transition of mesothelioma between epithelioid and sarcomatoid types may be reversible and regulated not by ERC/mesothelin, but by other unknown mechanisms.
Appendix
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Metadata
Title
Possible reversibility between epithelioid and sarcomatoid types of mesothelioma is independent of ERC/mesothelin expression
Authors
Masataka Kojima
Kazunori Kajino
Shuji Momose
Nadila Wali
May Thinzar Hlaing
Bo Han
Liang Yue
Masaaki Abe
Tomoaki Fujii
Katsuhisa Ikeda
Okio Hino
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Mesothelioma
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01449-2

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