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The role of CD44H molecule in the interactions between human monocytes and pancreatic adenocarcinoma-derived microvesicles
Affiliations- Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University Medical College, Krakow, Poland, Wielicka 265, 30-663 Kraków, Poland
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Abstract
Introduction. CD44H is a transmembrane molecule important for cell-cell and cell-extracellular matrix interactions. In monocytes, CD44H is implicated in phagocytosis of particles coated by hyaluronan (HA). HA fragments were shown to induce chemokine secretion by monocytes. Tumour derived microvesicles (TMVs), which are small membrane fragments derived from tumour cells can carry fragments of HA. The aim of the study was to examine whether monocyte’s CD44H is involved in the engulfment of pancreatic adenocarcinoma-derived microvesicles and in the production of chemokines induced by TMVs.
Materials and methods. TMVs engulfment and chemokines’ secretion stimulated with TMVs were determined in control human monocytes and cells incubated with anti-CD44H monoclonal antibody (mAb) by flow cytometry and ELISA, respectively. Phosphorylation of STAT3, transcription factor essential for chemokines’ production and CD44 signal transduction, was determined by Western blotting.
Results. Blocking of CD44H by anti-CD44H mAb on monocytes decreased the engulfment of TMVs and the
secretion of CCL4 and CCL5, but had no effect on CCL2, CCL3 and CXCL8. STAT-3 phosphorylation in
monocytes incubated with TMVs after CD44 blocking was also reduced.
Conclusion. The results suggest that tumour-derived microvesicles (TMVs) may carry bioactive cargo(s) which induces STAT3 dependent signalling pathway in human monocytes via CD44 molecules.
Abstract
Introduction. CD44H is a transmembrane molecule important for cell-cell and cell-extracellular matrix interactions. In monocytes, CD44H is implicated in phagocytosis of particles coated by hyaluronan (HA). HA fragments were shown to induce chemokine secretion by monocytes. Tumour derived microvesicles (TMVs), which are small membrane fragments derived from tumour cells can carry fragments of HA. The aim of the study was to examine whether monocyte’s CD44H is involved in the engulfment of pancreatic adenocarcinoma-derived microvesicles and in the production of chemokines induced by TMVs.
Materials and methods. TMVs engulfment and chemokines’ secretion stimulated with TMVs were determined in control human monocytes and cells incubated with anti-CD44H monoclonal antibody (mAb) by flow cytometry and ELISA, respectively. Phosphorylation of STAT3, transcription factor essential for chemokines’ production and CD44 signal transduction, was determined by Western blotting.
Results. Blocking of CD44H by anti-CD44H mAb on monocytes decreased the engulfment of TMVs and the
secretion of CCL4 and CCL5, but had no effect on CCL2, CCL3 and CXCL8. STAT-3 phosphorylation in
monocytes incubated with TMVs after CD44 blocking was also reduced.
Conclusion. The results suggest that tumour-derived microvesicles (TMVs) may carry bioactive cargo(s) which induces STAT3 dependent signalling pathway in human monocytes via CD44 molecules.
Keywords
CD44; human monocytes; HPC-4 cells; tumour-derived microvesicles; chemokines; STAT3 phosphorylation; flow cytometry
About this articleTitle
The role of CD44H molecule in the interactions between human monocytes and pancreatic adenocarcinoma-derived microvesicles
Journal
Folia Histochemica et Cytobiologica
Issue
Article type
Original paper
Pages
28-34
Published online
2019-04-04
Page views
2032
Article views/downloads
1419
DOI
Pubmed
Bibliographic record
Folia Histochem Cytobiol 2019;57(1):28-34.
Keywords
CD44
human monocytes
HPC-4 cells
tumour-derived microvesicles
chemokines
STAT3 phosphorylation
flow cytometry
Authors
Monika Baj-Krzyworzeka
Kazimierz Weglarczyk
Rafal Szatanek
Bozenna Mytar
Jaroslaw Baran
Maciej Siedlar
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