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Updated: Mar 27, 2026

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Bleb-based extravasation uses conserved morphodynamics but divergent calcium control.

Mizuki Morita1, Manami Morimoto1, Junichi Ikenouchi2

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Cell extravasation, essential for development and disease, utilizes calcium-dependent membrane blebs. The calcium source varies, with some cells using store-operated calcium entry (SOCE) and others using endoplasmic reticulum (ER) release.

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Area of Science:

  • Cell biology
  • Developmental biology
  • Cancer research

Background:

  • Extravasation is crucial for cell migration during development and in diseases like cancer metastasis.
  • Cellular exit from blood vessels involves complex morphodynamic processes.

Purpose of the Study:

  • To investigate the role of calcium (Ca²⁺) and membrane blebbing in cell extravasation across different cell types.
  • To identify the distinct calcium sources regulating bleb-based extravasation in primordial germ cells and cancer cells.

Main Methods:

  • Studied avian primordial germ cells (PGCs) and human cancer cell lines (HT-1080, PC-3, MDA-MB-231).
  • Observed transendothelial migration and formation of Ca²⁺-dependent membrane blebs.
  • Differentiated calcium sources: store-operated Ca²⁺ entry (SOCE) and IP₃R-mediated Ca²⁺ release from the endoplasmic reticulum (ER).

Main Results:

  • All examined extravasating cells formed Ca²⁺-dependent membrane blebs.
  • PGCs and HT-1080 cells utilized SOCE for Ca²⁺ supply.
  • Epithelial cancer cells (PC-3, MDA-MB-231) employed IP₃R-mediated Ca²⁺ release from the ER.
  • Identified distinct Ca²⁺ regulatory modules for bleb-based extravasation.

Conclusions:

  • Bleb-based extravasation is a conserved strategy with diverse Ca²⁺ regulatory mechanisms.
  • Evolutionarily, pathways trace back to ER release and SOCE.
  • Cancer cells co-opt developmental pathways, using both ER and SOCE, to enhance metastatic potential.
  • Ca²⁺ supply is a critical target for inhibiting cancer cell vascular escape and metastasis.