Interleukin 8 Receptors Govern Aggressiveness of Melanoma Tumors

Expansion and metastasis in melanoma have been linked to two receptor molecules that have been found to be overexpressed in this type of malignant skin cancer. Melanoma accounts for roughly 4% of all skin cancers, but is responsible for more than 74% of skin cancer deaths.

The two receptors bind to interleukin 8, which is a group of peptides produced by a variety of cell types that activate and recruit polymorphonuclear leukocytes in the inflammatory process, and are probably involved in initiation of labor and delivery in pregnant women. Interleukin 8 was abbreviated IL-8 but has been renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the Nomenclature Committee of the International Union of Immunological Societies.

The receptors, CXCR1 and CXCR2, are members of the G-protein-coupled receptor family. These proteins bind to CXCL8 with high affinity and transduce the signal through a G-protein activated second messenger system. In addition CXCR2 was found to bind to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth.

In the current study investigators at the University of Nebraska Medical Center (Omaha, USA) studied the link between the CXCL8 receptors and the aggressiveness of melanoma tumors. They used a mouse xenograft model to study the growth and expansion of melanoma cells that overexpressed CXCR1 and CXCR2.

Results published in the May 13, 2009, edition of the British Journal of Cancer revealed significantly increased tumor cell proliferation, increased microvessel density, and reduced apoptosis in tumors generated from CXCR1- or CXCR2-overexpressing melanoma cells.

"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," said senior author Dr. Rakesh Singh, professor of pathology and microbiology at the University of Nebraska Medical Center. "There is a possibility these molecules could be used in future therapy for melanoma -- something that does not exist at the moment."

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University of Nebraska Medical Center