Utah has the highest rate of melanoma in the United States. Melanoma is an aggressive skin cancer that spreads quickly. Factors including high altitude and a population that enjoys outdoor recreation, like skiing and hiking, contribute to high rates of melanoma among Utahns.
Allie Grossmann, MD, PhD, Huntsman Cancer Institute (HCI) researcher and assistant professor of pathology at the University of Utah (U of U), focuses on identifying better ways to treat this lethal cancer. In a recently published by the journal Cancer Research, Grossmann details one of the factors behind how and why melanoma metastasizes so quickly.
"Melanoma arises from the pigmentation cells of the skin. Those cells, called melanocytes, produce brown pigment to help protect our skin from sun damage. But melanocytes can transform into melanoma cells," explained Grossmann. Melanocytes have an inherent capacity to migrate all over the body and retain that ability following malignant transformation. Melanoma is able to spread to distant sites in the body earlier than most cancer cells.
The mechanism tumors use to spread around the body, or metastasize, is a hallmark of what makes cancers lethal. Early metastasis from primary tumors is a long-standing clinical conundrum in melanoma.
Grossmann wanted to know what drives melanoma cells to spread. Her study found that a protein called ARF6 contributes to early metastatic processes in melanoma. The most common form of melanoma is associated with changes in a cancer-causing gene known as BRAF that can signal the tumor to grow and spread to other areas of the body. Grossmann explained, "In general, we know that with melanoma and other cancers, the larger the primary tumor, the higher the chances of developing distant metastasis. However, activated ARF6 can promote metastasis independently of tumor size." The study also found that ARF6 facilitates the ability of tumor cells circulating in the bloodstream to invade and grow in distant organs.
"I think the takeaway from this study is that ARF activation is crucial for early melanoma spreading, regardless of tumor size" Grossmann said. She added that drugs targeting ARF6 are in preclinical development, making these agents potential options for future therapeutic use.
Grossmann would like to acknowledge the work of study collaborators in the , led by , HCI researcher and professor of surgery at the U of U, and the Odelberg Lab, led by , HCI researcher and assistant professor of internal medicine at the U of U.
The research is supported by the National Cancer Institute P30CA042014; National Institutes of Health; Melanoma Research Alliance; Harold J. Lloyd Charitable Trust; and Huntsman Cancer Foundation.