RRC ID 62957
著者 Kojima M, Kajino K, Momose S, Wali N, Hlaing MT, Han B, Yue L, Abe M, Fujii T, Ikeda K, Hino O.
タイトル Possible reversibility between epithelioid and sarcomatoid types of mesothelioma is independent of ERC/mesothelin expression.
ジャーナル Respir Res
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.
巻・号 21(1)
ページ 187
公開日 2020-7-16
DOI 10.1186/s12931-020-01449-2
PII 10.1186/s12931-020-01449-2
PMID 32677949
PMC PMC7364551
MeSH Animals Cell Differentiation* Cell Line, Tumor Epithelioid Cells / metabolism* Epithelioid Cells / pathology Female GPI-Linked Proteins / genetics GPI-Linked Proteins / metabolism* Gene Expression Regulation, Neoplastic Humans Mesothelin Mesothelioma / genetics Mesothelioma / metabolism* Mesothelioma / pathology Mice, Inbred BALB C Mice, Nude Oncogene Proteins / genetics Oncogene Proteins / metabolism* Phenotype Sarcoma / genetics Sarcoma / metabolism* Sarcoma / pathology Signal Transduction
IF 3.924
リソース情報
ヒト・動物細胞 ACC-MESO-4(RCB2293)