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High Mannose Binding Lectin (PFL) from Pseudomonas fluorescens Down-Regulates Cancer-Associated Integrins and Immune

Yuichiro Sato1, Kiminori Matsubara2, Takanori Kubo3

  • 1Department of Medical Pharmacy, Faculty of Pharmacy, Yasuda Women's University, Hiroshima 731-0153, Japan. sato-y@yasuda-u.ac.jp.

Cancers
|May 5, 2019
PubMed

Insights

Pseudomonas fluorescens lectin (PFL) triggers cancer cell death by degrading cell surface integrins and EGFR, leading to apoptosis. PFL also inhibits angiogenesis and down-regulates B7-H4, suggesting integrin interaction is key to its anti-cancer effects.

Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • Pseudomonas fluorescens lectin (PFL) is a high mannose-binding lectin.
  • PFL belongs to the OAAH (Oscillatoria agardhii agglutinin homologue) lectin family.
  • PFL has been shown to induce cancer cell death, but the mechanisms are unclear.

Purpose of the Study:

  • To elucidate the detailed mechanisms by which PFL induces cancer cell death.
  • To investigate the role of PFL in regulating cell surface molecules like integrins and EGFR.
  • To explore the impact of PFL on angiogenesis and T cell-mediated immunity.

Main Methods:

  • Cancer cell culture and treatment with PFL.
  • Analysis of integrin and EGFR expression and degradation.
  • Caspase-8 activity assay for apoptosis.
  • Ex vivo angiogenesis assay using rat aortic model.
  • B7-H4 expression analysis and siRNA silencing.
  • Surface plasmon resonance (SPR) for PFL-integrin interaction studies.

Main Results:

  • PFL decreased integrins and EGFR in cancer cells via internalization and autophagic degradation.
  • PFL induced caspase-8 dependent apoptosis.
  • PFL inhibited angiogenesis in a dose-dependent manner, linked to down-regulation of endothelium integrins.
  • PFL down-regulated B7-H4 in cancer cells, with evidence of association with β3 integrin.
  • SPR confirmed high-affinity, glycan-dependent binding of PFL to integrin αvβ3 and B7-H4.

Conclusions:

  • PFL-induced cancer cell death involves the degradation of integrins and EGFR, leading to apoptosis.
  • PFL exhibits anti-angiogenic properties potentially mediated by integrin down-regulation.
  • PFL's interaction with cell surface integrins, including αvβ3, and B7-H4 is crucial for its anti-cancer activities.
Keywords:
angiogenesisautophagyimmune checkpointintegrinlectin

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