A study by researchers at the John Wayne Cancer Institute at Saint John's Health Center has shown that a receptor protein found on melanoma cells appears to facilitate the disease's spread to the small intestine.
The study, published in the Feb. 1, 2008, issue of Clinical Cancer Research, also suggests that merging of the protein, called CCR9, with the CCL25 protein, which is known to play a role in the development of disease-fighting white blood cells, may help to explain the high incidence of melanoma metastasis to the lower bowel.
Melanoma is the most serious type of skin cancer, with more than 53,000 people in the U.S. diagnosed each year. Over the past three decades the percentage of people in the U.S. who develop this form of cancer has more than doubled. The disease is unique in that it metastasizes to the small intestine, where the spread of any other form of cancer is uncommon.
The study, “Activation of CCR9/CCL25 in Cutaneous Melanoma Mediates Preferential Metastasis to the Small Intestine,” was one of the largest of its kind to investigate the spread of melanoma to the gastrointestinal tract. It used various techniques, such as molecular biology, immunostaining and laboratory functional studies, to assess tumors for the two proteins; CCL25 is important because it often is produced in the small intestine—particularly during inflammation.
Results of the study showed CCR9 in 88 of 102 metastatic melanomas from the small intestine; in contrast, none of the 96 melanomas from other metastatic organ sites showed the CCR9 protein. Laboratory studies performed on CCR9-positive melanoma cells demonstrated metastatic properties in response to CCL25 that could be inhibited by specific chemical substances.
“We assessed tumor cells in the small intestine for CCR9 and demonstrated it with high significance compared with metastasis to other organs,” Hoon said. “Others, including our group, have demonstrated that certain cancers frequently spread to specific distant organs, often due to vascular drainage patterns, certain properties of organs, and anatomical location of the tumor origin site. What's unique here is that melanomas on or affecting the skin occur at multiple anatomical sites on the body and there's no direct vascular connection to the small intestine, yet the melanoma cells released from the primary tumor are attracted to this organ site.”
“The cell homing process involved is a well-developed biologic mechanism by which immune and inflammatory white blood cells move to specific sites during infection, inflammation or injury. The CCR9 receptor is revealed differentially via blood T lymphocytes to the small intestines. During inflammation of the small intestine, CCR9-positive lymphocytes are attracted. It appears that melanoma cells have hijacked the biological process of T lymphocytes to travel to the small intestine,” Hoon said.