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RETRACTED ARTICLE: Mesothelial cells differentiate into fibroblast-like cells under the scirrhous gastric cancer microenvironment and promote peritoneal carcinomatosis in vitro and in vivo

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This article was retracted on 01 December 2023

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Abstract

Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer (SGC), and myofibroblast provides a favorable environment for the peritoneal dissemination of gastric cancer. The aim of this study was to determine whether myofibroblast originates from peritoneal mesothelial cells under the influence of the tumor microenvironment. Immunohistochemical studies of peritoneal biopsy specimens from patients with peritoneal lavage cytological (+) status demonstrate the expression of the epithelial markers cytokeratin in fibroblast-like cells entrapped in the stroma, suggesting that these cells stemmed from local conversion of mesothelial cells. To confirm this hypothesis in vitro, we co-incubated mesothelial cells with SGC or non-SGC to investigate morphology and function changes. As we expected, mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype with loss of epithelial morphology and decrease in the expression of cytokeratin and E-cadherin when exposed to conditioned medium from HSC-39, and the induction of mesothelial cells can be abolished using a neutralizing antibody to transforming growth factor-beta1 (TGF-β1) as well as by pre-treatment with SB431542. Moreover, we found that these mesothelial cells-derived cells exhibit functional properties of myofibroblasts, including the ability to increase adhesion and invasion of SGC. In summary, our current data demonstrated that mesothelial cells are a source of myofibroblasts under the SGC microenvironment which provide a favorable environment for the dissemination of gastric cancer; TGF-β1 produced by autocrine/paracrine in peritoneal cavity may play a central role in this pathogenesis.

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Abbreviations

HPMCs:

Human peritoneal mesothelial cells

SGC:

Scirrhous gastric cancer

TGF-β1:

Transforming growth factor-beta1

SF-CM:

Serum-free conditional media

EMT:

Epithelial–mesenchymal transition

DMEM:

Dulbecco’s modified Eagle’s medium

FCS:

Fetal calf serum

PLC:

Peritoneal lavage cytological

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Nos.30873043, 30901419 and 81071956).

Conflict of interest

The authors declare that they have no competing interests exist.

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Correspondence to Hai-Bo Wang or Hui-Mian Xu.

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Lv, ZD., Wang, HB., Dong, Q. et al. RETRACTED ARTICLE: Mesothelial cells differentiate into fibroblast-like cells under the scirrhous gastric cancer microenvironment and promote peritoneal carcinomatosis in vitro and in vivo. Mol Cell Biochem 377, 177–185 (2013). https://doi.org/10.1007/s11010-013-1583-0

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  • DOI: https://doi.org/10.1007/s11010-013-1583-0

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