Is It Just a Mole, or Is It More?

"Photograph of melanoma on a patient's arm."

Photograph of melanoma on a patient's arm.

Fast and reliable tests that accurately detect and characterize cancer are a major goal in cancer research. At present, histological examination of the cells from a biopsy is the most cost-effective and widely used method for the diagnosis of melanoma. However, this traditional approach does not always reveal the extent of disease progression or adequately guide decisions about treatment strategies. New tests are currently being developed that can detect the proteins made by specific tumor cells and lead to more personalized and better treatment options. The tests that are now available have some drawbacks, which include low sensitivity and inability to detect all types of melanoma cells.

Toshihiko Hoashi, Ph.D., working with Vince Hearing, Ph.D., in the CCR Laboratory of Cell Biology, has been studying the cells that make melanin, which are called melanocytes, to identify new proteins that could be used to detect melanoma and more readily diagnose this quickly spreading disease. A protein called GPNMB was found in human melanoma cells, and Dr. Hoashi used cellular biology techniques to characterize the protein and assess its utility for the diagnosis of melanoma. A report of the findings was recently published in The FASEB Journal.

The researchers examined several different types of normal and cancerous melanocytic cells in cell culture and found that, unlike some proteins involved in melanin production, GPNMB is detectable in all melanocytes. The same result was obtained when human skin was evaluated. GPNMB is expressed in melanocytes, but not in other types of skin cells like keratinocytes or dermal fibroblasts. This finding suggests that the presence of GPNMB can be used to differentiate melanocytic cells from other cells in the skin.

Analysis of melanocytes showed that GPNMB is found in subcellular organelles called melanosomes, which produce melanin pigment. The protein was present in both early and late stages of melanosome development. There was more GPNMB expressed in the mature melanosomes, suggesting a role for the protein in the production of melanin. The protein was also secreted from the melanin-producing cells into the culture media. It was determined that the protein is first transported to the membrane of the cell, and then is cut off by cellular machinery. The role of the secreted GPNMB is not yet known.

While the role of GPNMB in melanocytes is still a mystery, characterization of the protein is a first step in the development of a possible new tool to aid in the identification and diagnosis of melanoma. Unlike the proteins that are currently tested for, GPNMB is present in all types of melanocytes and is also secreted outside of cells, which could be useful in a blood test for the disease. Thus, GPNMB may complement current molecular strategies being developed to identify melanoma and assess disease prognosis. The researchers are further evaluating the expression of GPNMB to determine how the expression levels change in tumor cells and in cells that have been exposed to UV radiation.

Summary Posted: Mon, 02/01/2010


FASEB J. 2010 Jan 8. [Epub ahead of print] PubMed Link