Scientists have uncovered a biological mechanism through which vitamin D can change the course of melanoma. They found that vitamin D influences a signaling pathway inside melanoma cells that helps them to thrive.
he researchers suggest that reducing the activity of the pathway could be a way to help the immune system fight this most dangerous of skin cancers.
While scientists have observed that people with melanoma fare less well if they have low levels of vitamin D, they have not known the reason.
The new Cancer Research study provides a molecular explanation.
“This new puzzle piece will help us better understand how melanoma grows and spreads, and hopefully find new targets to control it,” says Julia Newton-Bishop, a professor of dermatology at the University of Leeds in the United Kingdom.
“But what’s really intriguing,” she adds, “is that we can now see how vitamin D might help the immune system fight cancer.”
For the new study, Prof. Newton-Bishop and colleagues investigated the cell biology of vitamin D in melanoma. They began by looking at what happens when cells lack a protein known as a vitamin D receptor (VDR).
Vitamin D cannot send signals into cells unless the cells have VDRs on their surfaces.
It is the binding of the vitamin D molecule to its matching receptor that releases the signal into the cell.
So, to examine what happens in cells that lack VDR, the team studied the VDR gene that has the instructions for making the protein.
They investigated VDR in samples from 703 human melanoma tumors and in another 353 melanoma tumors that had spread from the original site.
They also looked for links between the gene’s activity and other features, including the thickness of the melanoma tumors and how fast they grew, together with any genetic alterations that might accompany faster tumor growth.
Following these investigations, the team then used mice to see how melanoma aggressiveness responded to changes in VDR levels.
The findings showed that human tumors grew more rapidly when their VDR gene expression was low. In addition, these tumors showed lower expression in genes that control pathways that promote immune activity against cancer cells.
The researchers also found that low VDR in tumors corresponded to higher expression of genes that promote cancer growth and spread.
One particularly noticeable gene cluster was the one that controls a signaling pathway called Wnt/β-catenin. This pathway has many cell functions, one of which is to promote growth.
In a further set of experiments on mice with melanoma, the researchers showed that they could reduce the activity of the Wnt/β-catenin pathway by raising VDR expression on the cancer cells. This manipulation also reduced the chances of the melanoma spreading to the animals’ lungs.