The Role of Vitamin D in the Development of Melanoma Established

Vitamin D may reduce the aggressiveness of melanoma cells and improve survival rates. This conclusion was reached by specialists at the British Cancer Research Center, who published their findings in the scientific journal Cancer Research.

Melanoma is the rarest but most deadly form of skin cancer: it accounts for the majority of fatalities among people with skin tumours. In the UK alone, this dangerous diagnosis is made annually for 16,000 patients, 300 of whom are diagnosed at an advanced stage. The insidiousness of melanoma lies in its tendency for rapid growth and metastasis, including to the lungs and brain. Such metastases are virtually untreatable, making the prognosis for individuals with advanced skin cancer extremely unfavorable.

New treatment methods developed over the past 40 years have doubled survival rates for melanoma. However, despite this, the survival rate at an advanced stage within the first year after diagnosis is only 55%, while early detection of the disease results in nearly 100%.

Vitamin D is a fat-soluble vitamin that performs a number of important functions in our body. Previous studies have shown that its deficiency in the blood is associated with less favorable outcomes in melanoma. Patients with this diagnosis often avoid sunlight to protect their skin from ultraviolet radiation, and therefore are at greater risk of vitamin D deficiency.

Conversely, higher levels of this vitamin correlate with less aggressive tumours and better treatment outcomes. However, the mechanism responsible for this relationship has remained unknown.

The Relationship Between Vitamin D Levels and Melanoma

To study this phenomenon, specialists from the University of Leeds conducted research to examine how vitamin D interacts with melanoma cells through the VDR receptors (vitamin D receptors) present on their surface.

First, the scientists investigated the expression level of the gene responsible for producing VDR receptors in 703 samples of common melanoma and 353 samples of tumours that had spread far beyond the primary site. They aimed to determine how actively this gene produced the VDR protein in melanoma cells. To do this, they counted the number of receptors on cells taken from each of these tumours.

They also noted and accounted for the thickness of each neoplasm and its growth rate. The team then compared the activity level of the gene responsible for synthesizing VDR proteins with the clinical characteristics of melanoma in each patient. As a result, they found a correlation between the number of receptors found in each cell, indicating the activity of the gene under investigation, and the aggressiveness of the tumour.

Signaling Pathway as the Key to the Puzzle

Researchers found that low levels of VDR gene expression were observed in tumours with a higher growth rate, regardless of whether they were primary or metastatic tumours. Furthermore, they concluded that low concentrations of vitamin D are apparently associated with the suppression of gene activity that regulates the body's anti-cancer immune response. In such neoplasms, there was a low number of immune cells, particularly infiltrating tumour lymphocytes.

Poor expression of the VDR gene was also linked to higher activity of genes responsible for rapid growth and spread of tumours, or in other words, genes that stimulate cancer aggressiveness. Specifically, genes that control the Wnt/β-catenin signaling pathway, a cellular signaling pathway that affects a variety of intracellular processes, including their growth.

Researchers also identified certain gene mutations in metastatic melanomas, such as deletion of the VDR gene and the addition of a methyl group to the promoter region of the gene. This hinders gene activity and consequently leads to an excessively low number of VDR receptors on these tumour cells.

To confirm these results, scientists repeated their study on mouse melanoma cells. It also showed that increased expression of the VDR gene in malignant cells suppresses the activity of the Wnt/β-catenin signaling pathway and reduces the growth and spread rate of the tumour. Finally, they found that vitamin D deficiency is associated with lower survival rates in primary tumours.

Thus, the experiments conducted by the British team confirmed that when the Wnt/β-catenin signaling pathway is active in melanoma cells, it suppresses the immune response, meaning the immune system's own fight against malignant cells, during which it destroys them before they can form a tumour.

This signaling pathway also promotes cell proliferation and tumour growth. Suppressing its activity by increasing the binding of vitamin D to its receptors improves immunity and reduces the growth rate of melanoma and its metastasis.

Main Conclusions

Scientists acknowledge that they are pleased with the results of their work, which provided them with insight into how vitamin D affects melanoma cells through VDR receptors, reducing the activity of the Wnt/β-catenin signaling pathway that stimulates tumour growth and spread. "This will help us better understand how melanoma grows and metastasizes, and hopefully will allow us to find new ways to control its course. Now we see how vitamin D can help the immune system fight cancer," says lead author of the study Julia Newton-Bishop.

"And although vitamin D alone does not cure cancer, now that we know how it works, we can use it to enhance the effectiveness of immunotherapy, which stimulates the patient's own immune system to recognize and attack malignant cells," she continues.

Martin Ledwick from the British Cancer Research Center noted that the National Health Service already recommends that people take 10 mcg of vitamin D daily to maintain musculoskeletal health, especially in winter when there is a lack of sunlight.

According to him, patients who have recently been diagnosed with melanoma should have their serum vitamin D levels tested, which will allow for better treatment planning. If it is found to be low, it is necessary to consult a doctor to prevent the negative consequences of this deficiency. Vitamin D levels can be increased by adjusting the diet and taking supplements.