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PDCD4 regulates apoptosis in human peritoneal mesothelial cells and promotes gastric cancer peritoneal metastasis

Pei Wu1, Jinou Wang2, Xiaoyun Mao3

  • 1Department of Surgical Oncology, Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.

Histology and Histopathology
|January 14, 2021
PubMed
Abstract

Insights

Decreased programmed cell death 4 (PDCD4) in human peritoneal mesothelial cells (HPMC) promotes gastric cancer metastasis. Transforming growth factor-beta 1 (TGF-β1) secreted by cancer cells may induce this apoptosis.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Mechanisms of Cancer

Background:

  • Programmed cell death 4 (PDCD4) is a tumor suppressor gene with incompletely understood functions.
  • The interplay between tumorigenesis and apoptosis is critical in cancer research.
  • Understanding PDCD4's role in peritoneal metastasis is essential.

Purpose of the Study:

  • To investigate the link between PDCD4-mediated apoptosis in human peritoneal mesothelial cells (HPMC) and gastric cancer peritoneal metastasis.
  • To explore the regulatory mechanisms of PDCD4 in this context.

Main Methods:

  • Assessed PDCD4 expression in HPMC and tumor tissues using immunohistochemistry and RT-PCR.
  • Utilized Transwell assays to monitor gastric cancer cell migration after PDCD4 silencing in HPMC.
  • Detected HPMC apoptosis via flow cytometry and western blotting.
  • Quantified cytokines, including transforming growth factor-beta 1 (TGF-β1), using ELISAs.
  • Analyzed PDCD4 expression and HPMC apoptosis following TGF-β1 treatment.

Main Results:

  • PDCD4 expression was significantly lower in human metastatic peritoneal tissues compared to normal tissues.
  • Reduced PDCD4 expression in HPMC correlated with increased gastric cancer cell migration.
  • Suppression of PDCD4 expression induced apoptosis in mesothelial cells, potentially regulated by TGF-β secreted from gastric cancer cells.

Conclusions:

  • Decreased PDCD4 expression in HPMC significantly promotes apoptosis, contributing to peritoneal metastasis in gastric cancer.
  • TGF-β1 secreted by gastric cancer cells appears to play a crucial role in this process.

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