Exploring differential connexin expression across melanocytic tumor progression involving the tumor microenvironment

Gergo Kiszner, Peter Balla, Barna Wichmann, G. Barna, Kornelia Baghy, Istvan Balazs Nemeth, Erika Varga, Istvan Furi, B. Tóth, T. Krenács

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number165
JournalCancers
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

Fingerprint

Connexins
Tumor Microenvironment
Connexin 43
Melanoma
Melanocytes
Neoplasms
Computer Simulation
Dysplastic Nevus Syndrome
Cell Line
Nevus
Epidermis
Membrane Proteins
Proteins
Coloring Agents
Down-Regulation
Polymerase Chain Reaction
Messenger RNA
Incidence

Keywords

  • Connexin isotype expression
  • Direct cell-cell communication
  • Gap junctions
  • Malignant melanoma
  • Melanocytic tumor progression
  • Melanoma microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Exploring differential connexin expression across melanocytic tumor progression involving the tumor microenvironment. / Kiszner, Gergo; Balla, Peter; Wichmann, Barna; Barna, G.; Baghy, Kornelia; Nemeth, Istvan Balazs; Varga, Erika; Furi, Istvan; Tóth, B.; Krenács, T.

In: Cancers, Vol. 11, No. 2, 165, 01.02.2019.

Research output: Contribution to journalArticle

Kiszner, Gergo ; Balla, Peter ; Wichmann, Barna ; Barna, G. ; Baghy, Kornelia ; Nemeth, Istvan Balazs ; Varga, Erika ; Furi, Istvan ; Tóth, B. ; Krenács, T. / Exploring differential connexin expression across melanocytic tumor progression involving the tumor microenvironment. In: Cancers. 2019 ; Vol. 11, No. 2.
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AU - Baghy, Kornelia

AU - Nemeth, Istvan Balazs

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AB - 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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