Electrical impulses between skin cells affect development of melanoma: Study

According to a study, the transfer of a neurotransmitter from one type of skin cell to another (melanocytes to keratinocytes) changed electrical activity and enhanced melanoma start in preclinical animals.

Washington [US], August 9 (ANI): According to a study, the transfer of a neurotransmitter from one type of skin cell to another (melanocytes to keratinocytes) changed electrical activity and enhanced melanoma start in preclinical animals. Skin cells called melanocytes, which contain melanin, give rise to the fatal skin disease known as melanoma. The capacity of melanocytes to produce vesicles carrying melanin to the keratinocytes that surround them is a fundamental characteristic that determines the colour of the skin.

BRAF gene alterations are prevalent in many benign skin lesions in addition to being present in around half of all melanomas. "This suggests that BRAF mutation is not sufficient for melanoma development and raises the question of why certain BRAF-mutated melanocytes develop into cancer, while others remain benign," said Richard White, MD, PhD, the senior author of the study and a physician-scientist at the University of Oxford Branch of the Ludwig Institute for Cancer Research and Memorial Sloan Kettering Cancer Center (MSK).

"Cancers exist within a community of cells from the onset," added first author Mohita Tagore, PhD, a postdoctoral research scientist at MSK. "We were interested in understanding how the community of skin cells contributes to melanoma development." White, Tagore, and colleagues investigated if communication between melanocytes and keratinocytes was involved in the development of benign BRAF-mutated melanocytes into melanoma since melanocytes are intricately entwined within a population of keratinocytes.

The researchers discovered that the transfer of molecules between BRAF-mutated melanocytes and healthy keratinocytes was essential for the onset of melanoma and that it happened almost exclusively between melanocytes and keratinocytes that were in close proximity to one another using zebrafish, mouse, and human cell models. Given that GABA signalling is normally associated with neurons rather than skin cells, the discovery that the neurotransmitter GABA was the mediator of this communication was a surprise, according to Tagore.

GABA prevents neurons from transmitting or receiving electrical impulses. Similar results were seen in skin cells, where the binding of released GABA to receptors on keratinocytes suppressed electrical activity and caused the production of a protein that promotes tumour growth. In addition, they discovered that melanoma cells expressed more GABA-producing genes than non-malignant melanocytes did.

The findings imply that BRAF-mutated melanocytes may upregulate and transmit GABA in order to reduce the electrical activity of nearby keratinocytes, permit the transfer of vesicles between the two cell types, and start the progression to melanoma, according to Tagore. She and her associates propose that chemicals transported by vesicles from melanocytes to keratinocytes may cause the keratinocytes to secrete the cancer-promoting protein. "Something about normal electrical activity in keratinocytes appears to suppress the progression of BRAF-mutated melanocytes to melanoma," she said. "Our findings indicate that some BRAF-mutated melanocytes are able to modulate this electrical activity through GABA in order to progress to melanoma.

"We typically consider electrical activity in the context of neuronal communication, but these observations implicate it in cancer development as well," Tagore added. "I would not have necessarily expected a neurotransmitter to be involved in the communication between skin cells," said White.

"Interactions between neurons and brain cancer cells have been reported, but here we observed neuronal-like communication occurring between two non-neuron cells." (ANI)

(This story has not been edited by Devdiscourse staff and is auto-generated from a syndicated feed.)