Lumican inhibits in vivo melanoma metastasis by altering matrix-effectors and invadopodia markers
| Autor: | Karamanou, Konstantina, Franchi, Marco, Proult, Isabelle, Rivet, Romain, Vynios, Demitrios, Brézillon, Stéphane |
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| Přispěvatelé: | Karamanou K., Franchi M., Proult I., Rivet R., Vynios D., Brezillon S., Laboratoire de Biochimie Médicale et Biologie Moléculaire, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), University of Patras [Patras], Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Lumican
Lung Neoplasms Skin Neoplasms [SDV.CAN]Life Sciences [q-bio]/Cancer Invadopodia Article Cell Movement Cell Line Tumor Epithelial-to-mesenchymal transi-tion Biomarkers Tumor Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Cyclin D1 Skin Neoplasm Neoplasm Metastasis Hyaluronic Acid Phosphorylation lcsh:QH301-705.5 Melanoma Cell Shape Cell Proliferation Focal Adhesions Animal lung metastasis Cell Cycle Snail Family Transcription Factor Lung metastasi Vinculin Extracellular Matrix Lung Neoplasm Mice Inbred C57BL Neoplasm Metastasi lcsh:Biology (General) Snail Podosomes Snail Family Transcription Factors epithelial-to-mesenchymal transition Focal Adhesion Cortactin Podosome Human Signal Transduction |
| Zdroj: | Cells Cells, MDPI, 2021, 10 (4), pp.841. ⟨10.3390/cells10040841⟩ Cells, Vol 10, Iss 841, p 841 (2021) Volume 10 Issue 4 |
| ISSN: | 2073-4409 |
| Popis: | It was reported that lumican inhibits the activity of metalloproteinase MMP-14 and melanoma cell migration in vitro and in vivo. Moreover, Snail triggers epithelial-to-mesenchymal transition and the metastatic potential of cancer cells. Therefore, the aim of this study was to examine the effect of lumican on Mock and Snail overexpressing melanoma B16F1 cells in vivo. Lung metastasis was analyzed after intravenous injections of Mock-B16F1 and Snail-B16F1 cells in Lum+/+ and Lum−/− mice. At day 14, mice were sacrificed, and lungs were collected. The number of lung metastatic nodules was significantly higher in mice injected with Snail-B16F1 cells as compared to mice injected with Mock-B16F1 cells confirming the pro-metastatic effect of Snail. This effect was stronger in Lum−/− mice as compared to Lum+/+, suggesting that endogenous lumican of wild-type mice significantly inhibits metastasis to lungs. Scanning electron and confocal microscopy investigations demonstrated that lumican inhibits the development of elongated cancer cell phenotypes which are known to develop invadopodia releasing MMPs. Moreover, lumican was shown to affect the expression of cyclin D1, cortactin, vinculin, hyaluronan synthase 2, heparanase, MMP-14 and the phosphorylation of FAK, AKT, p130 Cas and GSK3α/β. Altogether, these data demonstrated that lumican significantly inhibits lung metastasis in vivo, as well as cell invasion in vitro, suggesting that a lumican-based strategy targeting Snail-induced metastasis could be useful for melanoma treatment. |
| Databáze: | OpenAIRE |
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