Electrical signals between skin cells may affect melanoma initiation, shows study

The transfer of a neurotransmitter from one type of skin cell to another (melanocytes to keratinocytes) altered electrical activity and promoted melanoma initiation in preclinical models, according to results published in Cancer Discovery. An intrinsic feature of melanocytes is their ability to secrete melanin-containing vesicles to surrounding skin cells called keratinocytes to give skin its color. While approximately half of all melanomas harbor mutations in the BRAF gene, these mutations are present in many benign skin lesions as well.

Using zebrafish, mouse, and human cell models, the researchers observed that the transfer of molecules between BRAF-mutated melanocytes and normal keratinocytes was critical to melanoma initiation and that it occurred almost exclusively between melanocytes and keratinocytes that were in direct contact with one another.

Researchers discovered that this communication was mediated by the neurotransmitter GABA, which was an unexpected finding. In neurons, GABA inhibits a neuron’s ability to send or receive electrical signals. The researchers observed a similar effect in skin cells, as the binding of secreted GABA to receptors on keratinocytes inhibited electrical activity in keratinocytes and led to the secretion of a tumor-promoting protein.

In addition, they found that melanoma cells had increased expression of genes involved in GABA production compared with non-malignant melanocytes.

Reference: GABA regulates electrical activity and tumor initiation in melanoma, Cancer Discovery; DOI 10.1158/2159-8290.CD-23-0389