Researchers have recently demonstrated that BRAFV600E, a genetic mutation prevalent in metastatic melanoma, not only secretes proteins that enhance tumor growth, but also modifies surrounding cell networks to facilitate disease spread.
The study also demonstrates that treatment with vemurafenib may decrease the interaction between the tumor cells and the surrounding tissue, highlighting potential new therapy options.
Chery A Whipple from the Geisel School of Medicine at Dartmouth College and Constance Brinckerhoff from Geisel School of Medicine and the Dartmouth-Hitchcock Norris Cotton Cancer Center (both NH, USA) published their findings in the British Journal of Cancer.
Melanoma is one of the most lethal groups of skin cancer, responsible for upwards of 80% of all skin cancer deaths. This is primarily due to its rapid spread to other vital organs and lymph nodes, but if caught early, melanoma can often be treated effectively.
However, once the tumor enters the ‘vertical growth phase’, where it develops through different layers of the skin and often becomes metastatic, survival times can plummet to less than 9 months. Up to 50% of tumors exhibiting vertical growth phase characteristics have the BRAFV600E mutation, showing the relevance of this research.
The research utilized a new experimental protocol, which was reported by Brinckerhoff earlier this year. The new protocol enabled the researchers to study mouse melanoma cells in culture and in mice, affording extra experimental advantage.
Using this method, the researchers found that melanoma cells expressing BRAFV600E showed increased levels of certain cytokines and matrix metalloproteinase-1 (MMP-1). Cytokines have been shown to act on the immune system and help fight cancer, whereas MMPs are involved with tissue repair and metastasis.
From these findings, it appears as though there is a link between BRAFV600E and MMP-1, which modifies the cells surrounding melanoma tumors and improves the environment for tumor growth. As vemurafenib can specifically target the BRAFV600E mutation and reduce the expression of the proteins that activate this interaction, it offers new possibilities for the future treatment of melanoma.
“This work supports the importance of the tumor cells ‘talking’ with the normal cells present in the tumor microenvironment,” Whipple explained. “Targeting the tumor cells with specific therapy to reduce the secreted proteins can reduce the aggressive behavior of the tumor and inhibit disease progression.”