Next Article in Journal
Hypoxia Selectively Impairs CAR-T Cells In Vitro
Next Article in Special Issue
Integrins: Moonlighting Proteins in Invadosome Formation
Previous Article in Journal
Molecular Pathogenesis of Gene Regulation by the miR-150 Duplex: miR-150-3p Regulates TNS4 in Lung Adenocarcinoma
Previous Article in Special Issue
Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle

High Mannose Binding Lectin (PFL) from Pseudomonas fluorescens Down-Regulates Cancer-Associated Integrins and Immune Checkpoint Ligand B7-H4

1
Department of Medical Pharmacy, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, Japan
2
Department of Human Life Science Education, Graduate School of Education, Hiroshima University, Higashi-Hiroshima 739-8524, Japan
3
Department of Life Sciences, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, Japan
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, Japan
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 604; https://doi.org/10.3390/cancers11050604
Received: 29 March 2019 / Revised: 17 April 2019 / Accepted: 28 April 2019 / Published: 30 April 2019
(This article belongs to the Special Issue The Role of Integrins in Cancer)
  |  
PDF [1621 KB, uploaded 30 April 2019]
  |  

Abstract

Pseudomonas fluorescens lectin (PFL), which belongs to the high mannose (HM)-binding OAAH (Oscillatoria agardhii agglutinin homologue) lectin family, induces cancer cell death. However, the detailed mechanisms underlying this process have not yet been elucidated. We found that PFL decreased various integrins as well as EGFR in cancer cells by promoting internalization and autophagic degradation of these molecules, subsequently inducing caspase-8 dependent cell apoptosis. As revealed by an ex vivo angiogenesis assay using the rat aortic model, PFL inhibited neovascularization in a dose-dependent manner, which was potentially mediated by down-regulation of endothelium integrins. Interestingly, PFL also down-regulated B7-H4 in cancer cells, which has been implicated as a negative regulator of T cell-mediated immunity. We found that B7-H4 co-localized with β3 integrin in MKN28 gastric cancer cells. siRNA silencing of B7-H4 in MKN28 cells decreased expression of β3 integrin, suggesting physical and functional association between these molecules. Direct interaction of PFL with integrin αvβ3 or B7-H4 was examined by surface plasmon resonance analysis, which detected high affinity glycan-dependent binding to PFL. These investigations suggest that PFL interaction with cell surface integrins is a key process for the anti-cancer activities of PFL. View Full-Text
Keywords: lectin; integrin; autophagy; angiogenesis; immune checkpoint lectin; integrin; autophagy; angiogenesis; immune checkpoint
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Sato, Y.; Matsubara, K.; Kubo, T.; Sunayama, H.; Hatori, Y.; Morimoto, K.; Seyama, T. High Mannose Binding Lectin (PFL) from Pseudomonas fluorescens Down-Regulates Cancer-Associated Integrins and Immune Checkpoint Ligand B7-H4. Cancers 2019, 11, 604.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top