December 1, 2005

Researchers find mechanism that promotes malignant melanoma spread

By Elizabeth Crown

Researchers have discovered a key signaling mechanism that may promote the ability of highly aggressive malignant melanoma cells to metastasize, or spread from a primary tumor to distant sites in the body.

Results of their study, published in the November issue of Cancer Research, suggest that the signaling mechanism may be a potential target for prevention of metastatic melanoma.

The study was led by Angela R. Hess, a research scientist at the Children’s Memorial Research Center, and was conducted in the laboratory of Mary Hendrix, president and scientific director of the Children’s Memorial Research Center and professor of pediatrics at the Feinberg School of Medicine.

Metastatic cancer cells are characterized by increased tumor cell invasion and migration, as well as tumor cell plasticity, manifested as vasculogenic mimicry — the ability of aggressive melanoma cells to masquerade as endothelial-like cells by forming their own vascular networks.

Hess and co-investigators found that an enzyme known as focal adhesion kinase (FAK), which is important for many cellular processes, including cell survival, invasion and migration, is activated in malignant uveal (eye) and skin melanoma.

They hypothesized that FAK could play a major role in promoting aggressive melanoma because its increased production has been linked to tumor cell aggressiveness in other cancers, including prostate, thyroid, colorectal, ovarian and oral tumors.

Hess and colleagues found that elevated activity of FAK in aggressive melanoma cells correlated with the cells’ increased invasion, migration and vasculogenic mimicry behaviors.

As proof of principle, the researchers then blocked FAK signaling in aggressive melanoma cells, which resulted in a decrease in melanoma cell invasion, migration and vasculogenic mimicry.

“Collectively, our data suggest a new mechanism involved in promoting aggressive melanoma though FAK-mediated signal transduction pathways, thus providing new insights into possible therapeutic intervention strategies,” Hess said.

“Understanding the molecular mechanisms that promote aggressive melanoma is essential to predicting the likelihood of metastasis at a stage when intervention is possible,” Hess said.

The Hendrix laboratory has identified several signal transduction components that seem to play significant roles in mediating the aggressive properties of melanoma cells.