Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA.
Amides
/ pharmacology
Calcium
/ metabolism
Cell Communication
Cell Line, Tumor
Elastin
/ pharmacology
Extracellular Matrix Proteins
/ pharmacology
Extracellular Vesicles
/ physiology
HSP90 Heat-Shock Proteins
/ analysis
Heterocyclic Compounds, 4 or More Rings
/ pharmacology
Humans
Neoplasms
/ metabolism
Peptide Fragments
/ pharmacology
Pyridines
/ pharmacology
Receptors, Laminin
/ metabolism
Ribosomal Proteins
/ metabolism
Signal Transduction
rho-Associated Kinases
/ physiology
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
30
05
2018
accepted:
20
12
2018
revised:
06
12
2018
pubmed:
12
2
2019
medline:
31
10
2019
entrez:
12
2
2019
Statut:
ppublish
Résumé
Carcinogenesis occurs in elastin-rich tissues and leads to local inflammation and elastolytic proteinase release. This contributes to bioactive matrix fragment (Matrikine) accumulation like elastin degradation products (EDP) stimulating tumour cell invasive and metastatic properties. We previously demonstrate that EDPs exert protumoural activities through Hsp90 secretion to stabilised extracellular proteinases. EDP influence on cancer cell blebbing and extracellular vesicle shedding were examined with a videomicroscope coupled with confocal Yokogawa spinning disk, by transmission electron microscopy, scanning electron microscopy and confocal microscopy. The ribosomal protein SA (RPSA) elastin receptor was identified after affinity chromatography by western blotting and cell immunolocalisation. mRNA expression was studied using real-time PCR. SiRNA were used to confirm the essential role of RPSA. We demonstrate that extracellular matrix degradation products like EDPs induce tumour amoeboid phenotype with cell membrane blebbing and shedding of extracellular vesicle containing Hsp90 and proteinases in the extracellular space. EDPs influence intracellular calcium influx and cytoskeleton reorganisation. Among matrikines, VGVAPG and AGVPGLGVG peptides reproduced EDP effects through RPSA binding. Our data suggests that matrikines induce cancer cell blebbing and extracellular vesicle release through RPSA binding, favouring dissemination, cell-to-cell communication and growth of cancer cells in metastatic sites.
Sections du résumé
BACKGROUND
Carcinogenesis occurs in elastin-rich tissues and leads to local inflammation and elastolytic proteinase release. This contributes to bioactive matrix fragment (Matrikine) accumulation like elastin degradation products (EDP) stimulating tumour cell invasive and metastatic properties. We previously demonstrate that EDPs exert protumoural activities through Hsp90 secretion to stabilised extracellular proteinases.
METHODS
EDP influence on cancer cell blebbing and extracellular vesicle shedding were examined with a videomicroscope coupled with confocal Yokogawa spinning disk, by transmission electron microscopy, scanning electron microscopy and confocal microscopy. The ribosomal protein SA (RPSA) elastin receptor was identified after affinity chromatography by western blotting and cell immunolocalisation. mRNA expression was studied using real-time PCR. SiRNA were used to confirm the essential role of RPSA.
RESULTS
We demonstrate that extracellular matrix degradation products like EDPs induce tumour amoeboid phenotype with cell membrane blebbing and shedding of extracellular vesicle containing Hsp90 and proteinases in the extracellular space. EDPs influence intracellular calcium influx and cytoskeleton reorganisation. Among matrikines, VGVAPG and AGVPGLGVG peptides reproduced EDP effects through RPSA binding.
CONCLUSIONS
Our data suggests that matrikines induce cancer cell blebbing and extracellular vesicle release through RPSA binding, favouring dissemination, cell-to-cell communication and growth of cancer cells in metastatic sites.
Identifiants
pubmed: 30739912
doi: 10.1038/s41416-019-0382-0
pii: 10.1038/s41416-019-0382-0
pmc: PMC6461924
doi:
Substances chimiques
Amides
0
Extracellular Matrix Proteins
0
HSP90 Heat-Shock Proteins
0
Heterocyclic Compounds, 4 or More Rings
0
Peptide Fragments
0
Pyridines
0
RPSA protein, human
0
Receptors, Laminin
0
Ribosomal Proteins
0
Y 27632
138381-45-0
blebbistatin
20WC4J7CQ6
Elastin
9007-58-3
ROCK1 protein, human
EC 2.7.11.1
rho-Associated Kinases
EC 2.7.11.1
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
453-465Références
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