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J Cancer. 2017 Apr 09;8(7):1123-1128. doi: 10.7150/jca.18569. eCollection 2017.

Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas.

Journal of Cancer

Katanya C Alaga, Melissa Crawford, Lina Dagnino, Dale W Laird

Affiliations

  1. Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, Canada.
  2. Department of Physiology and Pharmacology, The University of Western Ontario, London, ON, Canada.

PMID: 28607585 PMCID: PMC5463425 DOI: 10.7150/jca.18569

Abstract

At present, it is unclear if melanocytes contain Cx43 gap junctions and whether Cx43 expression is regulated in melanoma onset and progression. To this end, we cultured pure populations of mouse melanocytes and found that they had no detectable Cx43 and exhibited an inability for dye transfer indicating they were devoid of functional gap junctions. Given the evidence that melanomas acquire the expression of other connexin isoforms during tumor progression, we assessed if Cx43 was also expressed and assembled into gap junctions at any stage of human melanoma onset and progression to distant metastases. Nearly all primary melanomas within the epidermis lacked Cx43. In contrast, nodal metastases expressed low levels of Cx43 which was markedly higher in distant metastases that had invaded vital organs. Importantly, in all stages of melanoma progression, Cx43 could be detected in intracellular compartments but was rarely assembled into gap junctions indicative of functional gap junction channels. Overall, these studies suggest that melanocytes do not form Cx43 homocellular gap junctions and even though Cx43 levels increase during melanoma progression, this connexin rarely assembles into gap junction structures.

Keywords: Cx43; connexin; gap junctional intercellular communication; gap junctions; melanoma.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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