FOXP3 expression and function in melanoma

© 2012 Dr. Bee Shin TanThe Forkhead boxP3 (FOXP3) transcription factor is a critical regulator of regulatory T (Treg) cell differentiation and immunosuppressive function. FOXP3 has also been reported to be expressed in many tumours, including melanoma. The role of FOXP3 in tumourigenesis is conflicting, with both tumour suppressive and tumour promoting functions described. In breast and prostate cancers loss of expression and inactivating mutations in FOXP3 suggest a tumour suppressor function. However, recent studies have failed to reproduce some of these findings. In pancreatic and urinary bladder cancer, over-expression of FOXP3 has been associated with immune suppression and poor outcome respectively, suggestive of a tumour promoting function. The aim of the current study was to determine the expression status and function of FOXP3 in melanoma. FOXP3 expression was detected in 12% (18/146) of metastatic melanomas analysed, but with low basal level of expression in a minor fraction of cells in melanoma cell lines. No mutations in FOXP3 were detected in a panel of 54 cell lines generated from patients with metastatic melanoma. To determine the effect of FOXP3 overexpression on the growth of melanoma cells, we stably over-expressed FOXP3 in the SKMEL-28 melanoma cell line, which normally expresses low levels of FOXP3. FOXP3 overexpression reduced the proliferation rate and clonogenecity of SK-MEL-28 melanoma cells in vitro and reduced tumour growth when grown as xenografts in vivo. FOXP3 overexpression also increased the rate of apoptosis and pigmentation of SK-MEL-28 melanoma cells, but did not lead to suppression of T-cell proliferation in co-culture experiments. Based on its infrequent expression in melanoma tumours, and its growth inhibitory and proapoptotic effect on melanoma cells, we conclude that FOXP3 is not a major driver of melanoma progression