Discovery of molecule ‘superfamily’ that causes melanoma apread

A University of Nebraska Medical Center research team has determined that a superfamily of molecules holds the secret to the progression and spread of melanoma -- the deadliest form of skin cancer. The study results were published in the May 13 of the British Journal of Cancer.

UNMC researcher Seema Singh, Ph.D., a research associate in the laboratory of Rakesh Singh, Ph.D., has investigated the roles of a superfamily of small molecules called 'chemokines' and their receptor 'partner molecules' in melanoma development.

Dr. Rakesh Singh's research team 'turned up' the normal activity of two particular receptor molecules called CXCR1 and CXCR2 inside human melanoma cell lines and studied the effect on cancer progression and tumor growth using a mouse model.

Their results suggested that CXCR1 and CXCR2 play key roles in the progression and spread of melanoma. The scientists found that the molecules helped tumor cells to grow. And when they 'turned up' the activity of CXCR1 and CXCR2 in healthy cells it triggered tumor formation.

Chemokines together with their receptor partner molecules control the movement of many types of cells in the body. Scientists already knew that some molecules from this superfamily regulated the movement of certain types of healthy cells in the body's lymphoid system and thought that chemokines also might control the migration of tumor cells in the body. Several studies have implicated CXCR1 and CXCR2 as important players in tumor progression.

Dr. Rakesh Singh, UNMC professor of pathology/microbiology and lead author, said the findings may lead to significant diagnostic and therapeutic advances.

"These results suggest that a superfamily of molecules controls whether a melanoma advances and spreads to other parts of the body -- when it becomes difficult to treat," Dr. Rakesh Singh said. "There is a possibility these molecules could be used in future therapy for melanoma -- something that doesn't exist at the moment."

Based on earlier research that he published in April's Clinical Cancer Research journal, Dr. Rakesh Singh knows these same receptors can play an important role in melanoma growth.

"We have evidence that they are good targets to inhibit growth," he said. "In cancer cells, these molecules may be over expressed and their function compromised."

"This important research gives us a start to understanding how malignant melanoma progresses and spreads," said Dr. Lesley Walker, director of cancer information at Cancer Research UK.

Melanoma accounts for roughly 4 percent of all skin cancers, but is responsible for more than 74 percent of skin cancer deaths.

Malignant melanoma is the most aggressive form of skin cancer with a very poor prognosis. The tumor originates in melanocytes, the cells which produce the pigment melanin that colours our skin, hair and eyes. If detected and treated early, it is easy to treat. But if it is ignored the cancer can advance and spread to other parts of the body, where it becomes hard to treat and can be fatal.

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