BRAF melanoma cells secrete factors that activate stromal fibroblasts

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BRAF mutations are thought to be a leading contributor to skin cancer which has been increasing year on year in the UK and the condition is now the most common form of cancer within the British population. In 2011, 13,348 people in the UK were diagnosed with malignant melanoma skin cancer (the most deadly form of the disease which is solely responsible for 80% of all skin cancer deaths).

Malignant melanoma is highly metastatic, reaching other organs by spreading through the lymph nodes. Previous studies have identified that the BRAF V600E gene is found to be mutated and results in constitutive activation of the mitogen-activated protein kinase pathway.

In new research published in 2014’s edition of the British Journal of Cancer(2), genetically engineered melanoma cell lines and xenograft mouse models were used to investigate how BRAF V600E affected cytokine (IL-1β, IL-6, and IL-8) and matrix metalloproteinase-1 (MMP-1) expression in tumour cells and in human dermal fibroblasts.

Results suggested that BRAF V600E melanoma cells secreted higher levels of the cytokines and MMP-1 than their wild-type counterparts. It was also found that the conditioned medium from the BRAF V600E melanoma cells activated the stromal fibroblasts, inducing expression of SDF-1 and its receptor CXCR4. This increase was mitigated when the conditioned medium was taken from melanoma cells treated with the BRAF V600E specific inhibitor, vemurafenib.

These results show that BRAF V600E plays a key role in activating the stroma and supports the theory that there is a mechanistic link between BRAF V600E and MMP-1 in mediating melanoma progression and in activating adjacent fibroblasts in the tumour microenvironment.

References:
1. Cancer Research
2. British Journal of Cancer

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