Study Finds Link Between Genetic Mutation and Melanoma Progression

Study Finds Link Between Genetic Mutation and Melanoma Progression

melanoma DNA testIn a study entitled, “BRAFV600E melanoma cells secrete factors that activate stromal fibroblasts and enhance tumourigenicity” published in the British Journal of Cancer, scientists from Dartmouth-Hitchcock Norris Cotton Cancer Center in New Hampshire have found that the genetic mutation BRAFV600E frequently found in metastatic melanoma not only secretes a protein that promotes the growth of tumor cells, but can also modify the network of normal cells surrounding the tumor, contributing to the disease’s progression.

The team used genetically modified melanoma cell lines and transplanted them into mouse models, observing that melanoma cells carrying the BRAFV600E mutation expressed higher levels of cytokines and Matrix Metalloproteinase-1 (MMP-1), an enzyme involved in tissue repair and metastasis.

Furthermore, the results showed that medium from melanoma cell carrying the BRAFV600E mutation promoted the activation of stromal fibroblasts, inducing the expression of stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 and making these fibroblasts more supportive of tumor growth and development.

Treating these cells with vemurafenib, a therapeutic drug that specifically targets the BRAFV600E mutation, was enough to reduce the expression of several proteins essential for activating this interaction, suggesting possible new treatment options for melanoma therapy.

“This work supports the importance of the tumor cells “talking” with the normal cells present in the tumor microenvironment. Targeting the tumor cells with specific therapy to reduce the secreted proteins can reduce the aggressive behavior of the tumor and inhibit disease progression.” Dr. Chery A. Whipple, research associate at the Geisel School of Medicine at Dartmouth and first author on the study, said in an Institute’s press release.

Melanoma is responsible for more than 80% of all skin cancer deaths and has a high metastatic potential, rapidly spreading to the lymph nodes and other organs.

The median survival times of metastatic melanoma is less than nine months, and this stage of advanced disease is often associated with the BRAFV600E mutation, found in about 50% of all melanomas and responsible for activating specific enzyme pathways involved in many different cell processes.

“Given that our data show that Vemurafenib is able to reduce the expression of several proteins that are essential for activating the tumor microenvironment (TME), a next step would be to ask whether Vemurafenib normalizes the TME, or keeps it from becoming activated. If so, does it create a window of time where we could target the TME, normalize it, and enhance the patient’s therapeutic response?” Whipple added in the press release.

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