Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.

Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation betw...

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Autores principales:	Jennifer Schmidt, Alexander Riechers, Raphael Stoll, Thomas Amann, Florian Fink, Thilo Spruss, Wolfram Gronwald, Burkhard König, Claus Hellerbrand, Anja Katrin Bosserhoff
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/39e4ad3f93ac47aba5e3380637e30990
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spelling	oai:doaj.org-article:39e4ad3f93ac47aba5e3380637e309902021-11-18T07:17:07ZTargeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.1932-620310.1371/journal.pone.0037941https://doaj.org/article/39e4ad3f93ac47aba5e3380637e309902012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22666418/?tool=EBIhttps://doaj.org/toc/1932-6203Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation between dimerization and functional activity. We subsequently identified the dodecapeptide AR71, which prevents MIA dimerization and thereby acts as a MIA inhibitor. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy demonstrated the binding of AR71 to the MIA dimerization domain, in agreement with in vitro and in vivo data revealing reduced cell migration, reduced formation of metastases and increased immune response after AR71 treatment. We believe AR71 is a lead structure for MIA inhibitors. More generally, inhibiting MIA dimerization is a novel therapeutic concept in melanoma therapy.Jennifer SchmidtAlexander RiechersRaphael StollThomas AmannFlorian FinkThilo SprussWolfram GronwaldBurkhard KönigClaus HellerbrandAnja Katrin BosserhoffPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37941 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jennifer Schmidt Alexander Riechers Raphael Stoll Thomas Amann Florian Fink Thilo Spruss Wolfram Gronwald Burkhard König Claus Hellerbrand Anja Katrin Bosserhoff Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.
description	Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation between dimerization and functional activity. We subsequently identified the dodecapeptide AR71, which prevents MIA dimerization and thereby acts as a MIA inhibitor. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy demonstrated the binding of AR71 to the MIA dimerization domain, in agreement with in vitro and in vivo data revealing reduced cell migration, reduced formation of metastases and increased immune response after AR71 treatment. We believe AR71 is a lead structure for MIA inhibitors. More generally, inhibiting MIA dimerization is a novel therapeutic concept in melanoma therapy.
format	article
author	Jennifer Schmidt Alexander Riechers Raphael Stoll Thomas Amann Florian Fink Thilo Spruss Wolfram Gronwald Burkhard König Claus Hellerbrand Anja Katrin Bosserhoff
author_facet	Jennifer Schmidt Alexander Riechers Raphael Stoll Thomas Amann Florian Fink Thilo Spruss Wolfram Gronwald Burkhard König Claus Hellerbrand Anja Katrin Bosserhoff
author_sort	Jennifer Schmidt
title	Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.
title_short	Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.
title_full	Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.
title_fullStr	Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.
title_full_unstemmed	Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.
title_sort	targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (mia) protein inhibition.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/39e4ad3f93ac47aba5e3380637e30990
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Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.

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