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Co-Conspirator Cells Contribute to Skin Cancer

Skin cancer is caused when cells grow out of control. But a new study finds there are previously unnoticed cells that help the cancer cells. The discovery of these co-conspirators, as they're being called, could eventually help predict, prevent and perhaps even stop melanoma before it spreads.

One in five Americans develops skin cancer over their lifetime, and melanoma is the most deadly form of skin cancer .

Changes in the body's pigment-producing cells, where melanoma takes hold are only part of the story, the new research finds. Other skin cells in what's called the microenvironment of the cancer site also play a key role, scientists say.

These adjacent cells, which are called keratinocytes, are actually the driver for the changes and malignant transformation in the pigment-producing cells, which are called melanocytes, said Arup Indra, an assistant professor in the Oregon State University College of Pharmacy.

So there are two avenues the pigment-producing cells where the cancer develops, and the adjacent skin cells which 'talk to' the pigment-producing cells in the form of signals, Indra said. They work in coordination, they are partners in crime.

The findings, announced today, are detailed in the journal Pigment Cell and Melanoma Research. It was funded by the National Institutes of Health.

Research was done with both animal models and human samples, from individuals who carry a mutation in a gene called Cdk4, which is an inherited predisposition to melanoma that has turned up in families in Norway, France, Australia and England.

The study found that a protein called RXR-alpha in skin keratinocytes appears to protect pigment cells from damage, and prevent them from progressing to invasive melanoma.

This protein in skin cells sends chemical signals to the adjacent pigment cells, Indra said. The study revealed that these signals can, in effect, prevent or block the abnormal proliferation of pigment-producing cells in laboratory mice. Conversely, when the protein was removed or repressed, melanoma cells became aggressive and invaded the animals' lymph nodes.

However, both the protective protein and pigment cells can suffer damage from chemical toxins or ultraviolet sunlight in the pigment cells, creating a double-edged sword in melanoma's complex etiology, according to Indra.

To study melanoma cells in isolation from their surrounding biochemical and molecular environment is to miss the intricate series of related interactions that give rise to the disease, he said.

The finding could lead to promising new prevention tools down the road, Indra said.

Better understanding this process will help us design new and novel strategies for prevention and, possibly, a cure, Indra said. This could be a predictive prognostic tool for discovering melanoma predisposition in humans. And that could lead to better and earlier diagnostics.