Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 14, Pages -Publisher
MDPI
DOI: 10.3390/ijms22147406
Keywords
EMILIN-1; small extracellular vesicles; metastasis; melanoma
Funding
- MINECO [SAF2014-54541-R]
- Ramon y Cajal Programme, Asociacion Espanola Contra el Cancer, La Caixa Foundation, Constantes y Vitales (ATRES MEDIA/AXA Foundation)
- FERO Foundation
- Translational NeTwork for the CLinical application of Extracellular VesicleS, TeNTaCLES [RED2018-102411-T(AEI/10.13039/501100011033)]
- MINECO-Severo Ochoa predoctoral program
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Studies have shown that melanoma-derived extracellular vesicles (EVs) play a role in lymph node metastasis, with EMILIN-1 being proteolyzed and secreted in small EVs as a mechanism to reduce its intracellular levels and promote metastasis in mouse melanoma lymph node metastatic cells. EMILIN-1 exhibits tumor and metastasis suppressive properties, reducing effective migration, cell viability, primary tumor growth, and metastasis.
Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.
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