Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas
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Updated: Feb 28, 2026
Experimental Metastasis Assay
Published on: August 24, 2010
Katanya C Alaga1, Melissa Crawford2, Lina Dagnino2
1Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, Canada.
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.
Insights
Melanocytes lack connexin 43 (Cx43) gap junctions. While Cx43 increases in melanoma progression, it rarely forms functional gap junctions, suggesting limited roles in tumor spread.
Area of Science:
- Cell Biology
- Cancer Research
- Dermatology
Background:
- Melanocytes, the cells responsible for skin pigmentation, are the cell of origin for melanoma.
- Connexins, particularly connexin 43 (Cx43), form gap junctions crucial for intercellular communication.
- The role of Cx43 in melanoma development and metastasis remains largely undetermined.
Purpose of the Study:
- To investigate Cx43 expression and gap junction formation in melanocytes and melanoma.
- To determine if Cx43 expression changes during melanoma progression from primary tumors to metastases.
- To assess the functional significance of Cx43 in melanoma.
Main Methods:
- Primary mouse melanocyte cultures were used to assess baseline Cx43 expression and function.
- Human melanoma tissues from various stages (primary, nodal metastases, distant metastases) were analyzed for Cx43.
- Immunohistochemistry and dye transfer assays were employed to evaluate Cx43 localization and gap junction activity.
Main Results:
- Normal melanocytes lack detectable Cx43 and functional gap junctions.
- Cx43 expression is absent in primary melanomas but increases in nodal and distant metastases.
- Despite increased Cx43 levels in advanced melanoma, it is predominantly found in intracellular compartments and rarely forms functional gap junctions.
Conclusions:
- Melanocytes do not form Cx43 homocellular gap junctions.
- Cx43 expression is upregulated during melanoma progression, but its assembly into functional gap junctions is limited.
- The observed intracellular localization of Cx43 suggests potential roles beyond canonical gap junction communication in melanoma metastasis.
