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Calcium-calpain Dependent Pathways Regulate Vesiculation in Malignant Breast Cells.

Jack Taylor1, Ritu Jaiswal1, Mary Bebawy2

  • 1Discipline of Pharmacy, Graduate School of Health, The University of Technology Sydney, NSW. Australia.

Current Cancer Drug Targets
|November 2, 2016
PubMed
Summary

Malignant cells exhibit higher membrane microparticle (MP) release due to calpain activity. Inhibiting calpain reduces MP formation, offering a potential strategy to target cancer cells and overcome multidrug resistance (MDR).

Keywords:
Atomic force microscopybreast cancercalciumcalpainextracellular vesiclesmicroparticlesmultidrug resistancevesiculation

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Area of Science:

  • Cell Biology
  • Cancer Research
  • Biochemistry

Background:

  • Multidrug resistance (MDR) in cancer is a significant challenge, often facilitated by cell-to-cell communication via membrane-derived microparticles (MPs).
  • MPs transfer functional molecules, contributing to MDR, metastasis, and angiogenesis.
  • Calpain, an intracellular protease, is crucial for MP formation by cleaving the cytoskeleton and inducing blebbing.

Purpose of the Study:

  • To investigate the role of calpain in membrane vesiculation in malignant and non-malignant cells.
  • To compare vesiculation at rest and after calcium release.
  • To assess the effect of calpain inhibitor II (ALLM) on vesiculation.

Main Methods:

  • Utilized high-resolution Atomic Force Microscopy (AFM) to analyze vesiculation.
  • Examined human brain endothelial cells (HBEC), mammary epithelial cells (MBE-F), MCF-7, and MCF-7/Dx cells.
  • Treated cells with calcium ionophore A23187 and calpain inhibitor II (ALLM).

Main Results:

  • Malignant cells (MCF-7, MCF-7/Dx) showed higher basal vesiculation than non-malignant cells (HBEC, MBE-F).
  • Calcium ionophore treatment increased vesiculation in all cell types.
  • Calpain inhibition significantly reduced vesiculation, indicating calpain-mediated MP biogenesis is dominant in malignant cells at rest.

Conclusions:

  • Significant differences in MP biogenic pathways exist between malignant and non-malignant cells.
  • Calpain plays a key role in MP formation in malignant cells.
  • Targeting calpain may offer novel strategies to circumvent MDR and other deleterious traits in cancer cells.