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Journal articles

Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA

Bertrand Brassart 1 Jordan da Silva 1 Mélissa Donet Emeline Seurat Frédéric Hague Christine Terryn 2 Frederic Velard 3 Jean Michel 4 Halima Ouadid-Ahidouch 5 Jean Monboisse Aleksander Hinek François-Xavier Maquart 6 Laurent Ramont 7 Sylvie Brassart 1
1 MEDyC - Matrice extracellulaire et dynamique cellulaire - UMR 7369
2 PICT - Plateforme en Imagerie Cellulaire et Tissulaire
URCA - Université de Reims Champagne-Ardenne, SFR CAP Santé (Champagne-Ardenne Picardie Santé)
3 BIOS - Biomatériaux et inflammation en site osseux - EA 4691
4 IMJ - Institut de Mathématiques de Jussieu
5 LPCM - Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667
6 SiRMa - Laboratoire de Signalisation et Récepteurs Matriciels
MEDyC - Matrice extracellulaire et dynamique cellulaire - UMR 7369
7 MERC - Matrice extracellulaire et régulations cellulaires
Abstract : 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.
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https://hal.univ-reims.fr/hal-02166734
Contributor : Jean-Marc Ferez Connect in order to contact the contributor
Submitted on : Thursday, June 27, 2019 - 10:29:08 AM
Last modification on : Tuesday, January 4, 2022 - 6:36:30 AM

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URCA | CNRS | MEDYC | LMR | SORBONNE-UNIVERSITE | UNIV-PARIS7 | USPC | UNIV-PARIS | UP-SCIENCES | SU-TI | U-PICARDIE | LPCM | IMJ | SU-SCIENCES | BIOS

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Bertrand Brassart, Jordan da Silva, Mélissa Donet, Emeline Seurat, Frédéric Hague, et al.. Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA. British Journal of Cancer, Cancer Research UK, 2019, 120 (4), pp.453-465. ⟨10.1038/s41416-019-0382-0⟩. ⟨hal-02166734⟩

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