Related Experiment Video

Updated: Jan 20, 2026

Measuring Calpain Activity in Fixed and Living Cells by Flow Cytometry
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Measuring Calpain Activity in Fixed and Living Cells by Flow Cytometry

Published on: July 8, 2010

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Preventing Calpain Externalization by Reducing ABCA1 Activity with Probenecid Limits Melanoma Angiogenesis and

Guillaume Hanouna1, Ellie Tang1, Joëlle Perez1

  • 1Sorbonne Universités, Université Pierre et Marie Curie, Univ Paris 06, UMR_S 1155 and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; Institut National de la Santé et de la Recherche Médicale, UMR_S 1155, Paris, France.

The Journal of Investigative Dermatology
|August 20, 2019
PubMed

Insights

Blocking extracellular calpains limits melanoma growth. Inhibiting the ATP-binding cassette transporter A1 (ABCA1) reduces tumor neoangiogenesis and invasiveness, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Calpains are intracellular proteases crucial for neoangiogenesis, tumor invasiveness, and metastasis.
  • Calpains are partially exteriorized through the ATP-binding cassette transporter A1 (ABCA1), but their extracellular role in tumor growth is unclear.

Purpose of the Study:

  • To investigate the role of extracellular calpains in melanoma progression.
  • To evaluate the impact of blocking calpain exteriorization or activity on tumor growth and neoangiogenesis.

Main Methods:

  • Utilized a B16-F10 melanoma model in transgenic mice overexpressing extracellular calpastatin.
  • Administered probenecid to wild-type mice to inhibit ATP-binding cassette transporter A1 (ABCA1) activity.
  • Performed in vitro cytotoxicity assays and in vivo tumor studies, including endothelial cell migration and capillary formation assays.

Main Results:

  • Transgenic mice with high extracellular calpastatin showed a ~3-fold inhibition in tumor growth compared to wild-type.
  • Probenecid treatment also resulted in a ~3-fold inhibition of melanoma tumor growth.
  • Both interventions led to defects in tumor neoangiogenesis, reduced endothelial cell migration, and capillary formation.

Conclusions:

  • Extracellular calpains contribute significantly to melanoma neoangiogenesis and invasiveness.
  • Inhibiting ATP-binding cassette transporter A1 (ABCA1) activity effectively reduces melanoma tumor growth by limiting calpain exteriorization and neoangiogenesis.
  • Targeting extracellular calpain activity presents a potential therapeutic strategy for melanoma treatment.

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