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Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment

The incidence of malignant melanoma, one of the deadliest cancers, continues to increase. Here we tested connexin (Cx) expression in primary melanocytes, melanoma cell lines and in a common nevus, dysplastic nevus, and thin, thick, and metastatic melanoma tumor progression series involving the tumor...

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Autores principales: Kiszner, Gergo, Balla, Peter, Wichmann, Barna, Barna, Gabor, Baghy, Kornelia, Nemeth, Istvan Balazs, Varga, Erika, Furi, Istvan, Toth, Bela, Krenacs, Tibor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406766/
https://www.ncbi.nlm.nih.gov/pubmed/30717194
http://dx.doi.org/10.3390/cancers11020165
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author Kiszner, Gergo
Balla, Peter
Wichmann, Barna
Barna, Gabor
Baghy, Kornelia
Nemeth, Istvan Balazs
Varga, Erika
Furi, Istvan
Toth, Bela
Krenacs, Tibor
author_facet Kiszner, Gergo
Balla, Peter
Wichmann, Barna
Barna, Gabor
Baghy, Kornelia
Nemeth, Istvan Balazs
Varga, Erika
Furi, Istvan
Toth, Bela
Krenacs, Tibor
author_sort Kiszner, Gergo
collection PubMed
description The incidence of malignant melanoma, one of the deadliest cancers, continues to increase. Here we tested connexin (Cx) expression in primary melanocytes, melanoma cell lines and in a common nevus, dysplastic nevus, and thin, thick, and metastatic melanoma tumor progression series involving the tumor microenvironment by utilizing in silico analysis, qRT-PCR, immunocyto-/histochemistry and dye transfer tests. Primary melanocytes expressed GJA1/Cx43, GJA3/Cx46 and low levels of GJB2/Cx26 and GJC3/Cx30.2 transcripts. In silico data revealed downregulation of GJA1/Cx43 and GJB2/Cx26 mRNA, in addition to upregulated GJB1/Cx32, during melanoma progression. In three melanoma cell lines, we also showed the loss of GJA1/Cx43 and the differential expression of GJB1/Cx32, GJB2/Cx26, GJA3/Cx46 and GJC3/Cx30.2. The dominantly paranuclear localization of connexin proteins explained the ~10–90 times less melanoma cell coupling compared to melanocytes. In melanocytic tumor tissues, we confirmed the loss of Cx43 protein, fall of cell membrane and elevated paranuclear Cx32 with moderately increased cytoplasmic Cx26 and paranuclear Cx30.2 positivity during tumor progression. Furthermore, we found Cx43, Cx26 and Cx30 proteins upregulated in the melanoma adjacent epidermis, and Cx43 in the tumor flanking vessels. Therefore, differential connexin expression is involved in melanocytic tumor progression where varying connexin isotypes and levels reflect tumor heterogeneity-related bidirectional adaptive interactions with the microenvironment.
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spelling pubmed-64067662019-03-21 Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment Kiszner, Gergo Balla, Peter Wichmann, Barna Barna, Gabor Baghy, Kornelia Nemeth, Istvan Balazs Varga, Erika Furi, Istvan Toth, Bela Krenacs, Tibor Cancers (Basel) Article The incidence of malignant melanoma, one of the deadliest cancers, continues to increase. Here we tested connexin (Cx) expression in primary melanocytes, melanoma cell lines and in a common nevus, dysplastic nevus, and thin, thick, and metastatic melanoma tumor progression series involving the tumor microenvironment by utilizing in silico analysis, qRT-PCR, immunocyto-/histochemistry and dye transfer tests. Primary melanocytes expressed GJA1/Cx43, GJA3/Cx46 and low levels of GJB2/Cx26 and GJC3/Cx30.2 transcripts. In silico data revealed downregulation of GJA1/Cx43 and GJB2/Cx26 mRNA, in addition to upregulated GJB1/Cx32, during melanoma progression. In three melanoma cell lines, we also showed the loss of GJA1/Cx43 and the differential expression of GJB1/Cx32, GJB2/Cx26, GJA3/Cx46 and GJC3/Cx30.2. The dominantly paranuclear localization of connexin proteins explained the ~10–90 times less melanoma cell coupling compared to melanocytes. In melanocytic tumor tissues, we confirmed the loss of Cx43 protein, fall of cell membrane and elevated paranuclear Cx32 with moderately increased cytoplasmic Cx26 and paranuclear Cx30.2 positivity during tumor progression. Furthermore, we found Cx43, Cx26 and Cx30 proteins upregulated in the melanoma adjacent epidermis, and Cx43 in the tumor flanking vessels. Therefore, differential connexin expression is involved in melanocytic tumor progression where varying connexin isotypes and levels reflect tumor heterogeneity-related bidirectional adaptive interactions with the microenvironment. MDPI 2019-02-01 /pmc/articles/PMC6406766/ /pubmed/30717194 http://dx.doi.org/10.3390/cancers11020165 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kiszner, Gergo
Balla, Peter
Wichmann, Barna
Barna, Gabor
Baghy, Kornelia
Nemeth, Istvan Balazs
Varga, Erika
Furi, Istvan
Toth, Bela
Krenacs, Tibor
Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment
title Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment
title_full Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment
title_fullStr Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment
title_full_unstemmed Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment
title_short Exploring Differential Connexin Expression across Melanocytic Tumor Progression Involving the Tumor Microenvironment
title_sort exploring differential connexin expression across melanocytic tumor progression involving the tumor microenvironment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406766/
https://www.ncbi.nlm.nih.gov/pubmed/30717194
http://dx.doi.org/10.3390/cancers11020165
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