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Updated: Jul 22, 2025

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Extracellular Leakage Protein Patterns in Two Types of Cancer Cell Death: Necrosis and Apoptosis

Akira Sato1, Akira Shimotsuma1, Tetsuya Miyoshi1

  • 1Department of Biochemistry and Molecular Biology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan.

ACS Omega
|July 24, 2023
PubMed

Insights

Cancer cells undergoing necrosis or apoptosis release extracellular proteins. This study reveals that the secretome, or extracellular proteome, plays a role in regulating these distinct cell death pathways.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Cell death, including necrosis and apoptosis, is crucial in cancer development.
  • Dead cells release extracellular DNA, RNA, and proteins.

Purpose of the Study:

  • To investigate the role of the extracellular proteome (secretome) in regulating necrosis and apoptosis.
  • To analyze the secretome changes in mouse tumor cells treated with floxuridine (FUdR).

Main Methods:

  • Treatment of mouse tumor FM3A cells (original strain F28-7 and variant F28-7-A) with the anticancer drug floxuridine (FUdR).
  • Shotgun proteomic analysis to profile the extracellular secretome.
  • Analysis of protein leakage involved in signal transduction, transcription, RNA processing, translation, and cell death.

Main Results:

  • FUdR induced necrosis in the F28-7 strain and apoptosis in the F28-7-A variant.
  • Altered protein leakage in the secretome was associated with signal transduction, transcription, RNA processing, translation, and cell death.
  • High mobility group box 1 and 2 proteins were detected in both necrotic and apoptotic cell culture media.

Conclusions:

  • The extracellular secretome is involved in mediating distinct cell death phenomena like necrosis and apoptosis.
  • Secretory proteins may play unique roles in the regulation of cancer cell death pathways.

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