Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.

Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of the patients, with a high lethality rate. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the...

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Autores principales: Rosaria Gangemi, Valentina Mirisola, Gaia Barisione, Marina Fabbi, Antonella Brizzolara, Francesco Lanza, Carlo Mosci, Sandra Salvi, Marina Gualco, Mauro Truini, Giovanna Angelini, Simona Boccardo, Michele Cilli, Irma Airoldi, Paola Queirolo, Martine J Jager, Antonio Daga, Ulrich Pfeffer, Silvano Ferrini
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:8794d72c7aff40deaffe0b6d143e06642021-11-18T07:30:15ZMda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.1932-620310.1371/journal.pone.0029989https://doaj.org/article/8794d72c7aff40deaffe0b6d143e06642012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22267972/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of the patients, with a high lethality rate. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiles of primary human uveal melanomas showed high expression of SDCBP gene (encoding for syndecan-binding protein-1 or mda-9/syntenin), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent datasets of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of mda-9/syntenin protein in primary tumors was significantly related to metastatic recurrence in our cohort of patients. Mda-9/syntenin expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumors. Interestingly, mda-9/syntenin showed both cytoplasmic and nuclear localization in cell lines and in a fraction of patients, suggesting its possible involvement in nuclear functions. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2Rγ null mice and the study of mda-9/syntenin expression in primary and metastatic lesions revealed higher mda-9/syntenin in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a wound-healing assay. Moreover, silencing of SDCBP in mda-9/syntenin-high uveal melanoma cells inhibited the hepatocyte growth factor (HGF)-triggered invasion of matrigel membranes and inhibited the activation of FAK, AKT and Src. Conversely syntenin overexpression in mda-9/syntenin-low uveal melanoma cells mediated opposite effects. These results suggest that mda-9/syntenin is involved in uveal melanoma progression and that it warrants further investigation as a candidate molecular marker of metastases and a potential therapeutic target.Rosaria GangemiValentina MirisolaGaia BarisioneMarina FabbiAntonella BrizzolaraFrancesco LanzaCarlo MosciSandra SalviMarina GualcoMauro TruiniGiovanna AngeliniSimona BoccardoMichele CilliIrma AiroldiPaola QueiroloMartine J JagerAntonio DagaUlrich PfefferSilvano FerriniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29989 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rosaria Gangemi
Valentina Mirisola
Gaia Barisione
Marina Fabbi
Antonella Brizzolara
Francesco Lanza
Carlo Mosci
Sandra Salvi
Marina Gualco
Mauro Truini
Giovanna Angelini
Simona Boccardo
Michele Cilli
Irma Airoldi
Paola Queirolo
Martine J Jager
Antonio Daga
Ulrich Pfeffer
Silvano Ferrini
Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
description Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of the patients, with a high lethality rate. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiles of primary human uveal melanomas showed high expression of SDCBP gene (encoding for syndecan-binding protein-1 or mda-9/syntenin), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent datasets of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of mda-9/syntenin protein in primary tumors was significantly related to metastatic recurrence in our cohort of patients. Mda-9/syntenin expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumors. Interestingly, mda-9/syntenin showed both cytoplasmic and nuclear localization in cell lines and in a fraction of patients, suggesting its possible involvement in nuclear functions. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2Rγ null mice and the study of mda-9/syntenin expression in primary and metastatic lesions revealed higher mda-9/syntenin in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a wound-healing assay. Moreover, silencing of SDCBP in mda-9/syntenin-high uveal melanoma cells inhibited the hepatocyte growth factor (HGF)-triggered invasion of matrigel membranes and inhibited the activation of FAK, AKT and Src. Conversely syntenin overexpression in mda-9/syntenin-low uveal melanoma cells mediated opposite effects. These results suggest that mda-9/syntenin is involved in uveal melanoma progression and that it warrants further investigation as a candidate molecular marker of metastases and a potential therapeutic target.
format article
author Rosaria Gangemi
Valentina Mirisola
Gaia Barisione
Marina Fabbi
Antonella Brizzolara
Francesco Lanza
Carlo Mosci
Sandra Salvi
Marina Gualco
Mauro Truini
Giovanna Angelini
Simona Boccardo
Michele Cilli
Irma Airoldi
Paola Queirolo
Martine J Jager
Antonio Daga
Ulrich Pfeffer
Silvano Ferrini
author_facet Rosaria Gangemi
Valentina Mirisola
Gaia Barisione
Marina Fabbi
Antonella Brizzolara
Francesco Lanza
Carlo Mosci
Sandra Salvi
Marina Gualco
Mauro Truini
Giovanna Angelini
Simona Boccardo
Michele Cilli
Irma Airoldi
Paola Queirolo
Martine J Jager
Antonio Daga
Ulrich Pfeffer
Silvano Ferrini
author_sort Rosaria Gangemi
title Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
title_short Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
title_full Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
title_fullStr Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
title_full_unstemmed Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
title_sort mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/8794d72c7aff40deaffe0b6d143e0664
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