Investigation of female survival benefit in metastatic melanoma

Epidemiological studies show female survival benefit in advanced metastatic melanoma. In investigating a possible mechanism for this female survival b enefit, we have previously reported that the female steroid 17 beta-oestrad iol significantly reduces invasion of a human melanoma cell line (A375-SM c ells) and ocular melanoma cells through fibronectin. Neither cell type was found to possess oestrogen receptor-alpha. The aim of the current study was to obtain further information on the extent to which progression of cutane ous melanoma might be sex steroid sensitive by (a) examining the relationsh ip between circulating sex steroids, sex hormone binding globulin and disea se progression; (b) examining the relationship between sex steroid structur e and the ability of steroids to reduce invasion of a melanoma cell line in vitro; and (c) examining the effects of sex steroids on proliferation of t hese cells in vitro. We report a significant reduction in circulating oestr one with disease progression in male but not female patients. Examining ste roids for their ability to inhibit invasion of A375-SM cells through fibron ectin in vitro, oestrogenic compounds (17 beta-oestradiol and oestrone) wer e found to inhibit invasion; in this respect, oestrone was approximately 50 times more potent than 17 beta-oestradiol; steroids lacking the benzene ri ng structure did not inhibit invasion, indeed dehydroepiandrosterone (DHEA) which acts as a precursor to androgenic steroids significantly enhanced in vasion. Proliferation of A375-SM cells was unaffected by 17 beta-oestradiol , oestrone or dihydrotestosterone when cells were cultured on plastic; in c ontrast, all three steroids induced modest proliferation of cells when grow n on fibronectin with dihydrotestosterone the most mitogenic of the three s teroids. These data are consistent with sex steroids playing a role in mela noma progression.