British researchers have found that vitamin D helps fight a serious form of skin cancer known as melanoma. In a study published in the journal Cancer Research, they reported that increasing vitamin D levels can help suppress a signaling pathway linked to the growth and spread of melanoma cells.

“[What’s] really intriguing is that we can now see how vitamin D might help the immune system fight cancer,” said Julia Newton-Bishop, a professor of dermatology at the University of Leeds and one of the study researchers.

Increasing Vitamin D receptor expression increases immune activity against melanoma

Melanoma is a form of skin cancer that begins in cells known as melanocytes. While less common than basal cell carcinoma and squamous cell carcinoma, it is more dangerous because it spreads more easily to other organs if left untreated at an early stage. In the United States, nearly 7,000 people die from melanoma every year, while only 2,000 die from basal and squamous cell carcinoma.

Past studies have linked low levels of vitamin D in the body to a worse melanoma outcome. But the precise mechanisms behind this had been unclear. To that end, Newton-Bishop and her team investigated what happens when cells lack a protein called vitamin D receptor (VDR). Vitamin D cannot bind to cells unless the cells have VDRs on their surfaces.

The researchers obtained samples from 703 human melanoma tumors and 353 metastatic ones (tumors that have spread from the original site) to study the expression of the gene that has the instructions for making VDR. Within these samples, they looked for links between the gene’s expression and other features, such as the thickness of the melanoma tumors, how fast they grew and genetic alterations that caused faster tumor growth.

The researchers found that human tumors with low VDR gene expression grew more rapidly and displayed reduced expression of proteins involved in promoting immune-mediated anti-cancer activity. Low VDR expression also corresponded to higher expression of genes that promote the growth and spread of cancer, particularly a gene cluster that controls a signaling pathway called Wnt/Beta-catenin.

“We know when the Wnt/Beta-catenin pathway is active in melanoma, it can dampen down the immune response, causing fewer immune cells to reach the inside of the tumor, where they could potentially fight the cancer better,” explained Newton-Bishop.

In a separate experiment with mice, the team found that increasing VDR expression on melanoma cells reduced the activity of the Wnt/Beta-catenin pathway and slowed down tumor growth. This also lessened the spread of melanoma cells to the lungs. These findings point to new ways of using vitamin D to reduce Wnt/Beta-catenin pathway activity and boost the immune system’s ability to fight melanoma. According to a study published in Calcified Tissue International, supplementing with vitamin D is a great way to increase VDR expression in human cells.

“This new puzzle piece will help us better understand how melanoma grows and spreads, and hopefully find new targets to control it,” said Newton-Bishop. “Although vitamin D on its own won’t treat cancer, we could take insights from the way it works to boost the effects of immunotherapy, which uses the immune system to find and attack cancer cells.”