Overexpression of connexin 43 reduces melanoma proliferative and metastatic capacity
Background: Alterations in connexin 43 (Cx43) expression and/or gap junction (GJ)-mediated intercellular communication are implicated in cancer pathogenesis. Herein, we have investigated the role of Cx43 in melanoma cell proliferation and apoptosis sensitivity in vitro , as well as metastatic capabi...
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Veröffentlicht in: | British journal of cancer 2015-07, Vol.113 (2), p.259-267 |
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Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Background:
Alterations in connexin 43 (Cx43) expression and/or gap junction (GJ)-mediated intercellular communication are implicated in cancer pathogenesis. Herein, we have investigated the role of Cx43 in melanoma cell proliferation and apoptosis sensitivity
in vitro
, as well as metastatic capability and tumour growth
in vivo
.
Methods:
Connexin 43 expression levels, GJ coupling and proliferation rates were analysed in four different human melanoma cell lines. Furthermore, tumour growth and lung metastasis of high compared with low Cx43-expressing FMS cells were evaluated
in vivo
using a melanoma xenograft model.
Results:
Specific inhibition of Cx43 channel activity accelerated melanoma cell proliferation, whereas overexpression of Cx43 increased GJ coupling and reduced cell growth. Moreover, Cx43 overexpression in FMS cells increased basal and tumour necrosis factor-
α
-induced apoptosis and resulted in decreased melanoma tumour growth and lower number and size of metastatic foci
in vivo
.
Conclusions:
Our findings reveal an important role for Cx43 in intrinsically controlling melanoma growth, death and metastasis, and emphasise the potential use of compounds that selectively enhance Cx43 expression on melanoma in the future chemotherapy and/or immunotherapy protocols. |
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ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/bjc.2015.162 |