Epidemiological data showing survival advantage in female melanoma patients suggest the influence of endocrine factors on the clinical course of the disease. These data were supported by our previous experimental studies demonstrating higher liver colonization potential of intrasplenically injected human melanoma cells in male than in female SCID mice. However, such difference could not be observed in lung colonization after intravenous injection. The aim of our present study was to examine the metastatic pattern of human melanoma cells injected intracardially in the left ventricle, and to determine the possible differences between male and female mice. Moreover, using two human melanoma lines (HT168-M1, HT199), metastasis formation after intracardiac injection in previously castrated SCID mice was compared to that of intact animals. The melanoma lines developed metastases in the adrenals, kidneys, bones, brain and heart in 90-100% of the animals, with no significant differences in the incidence between the sexes, or between castrated and intact animals, either males or females. However, significantly more liver metastases were produced in sham-operated than in orchiectomized male mice, or in females (either castrated or intact). On the other hand, a higher number of liver metastases was observed in ovariectomized females compared to sham-operated ones in the case of HT199 line, and a similar, although statistically not significant trend was seen in the case of HT168-M1 line. These data indicate that gender differences in melanoma progression in this animal model are organ-dependent, with a preferential involvement of the liver. The mechanisms of sex-dependent metastatization of human melanomas, or its organ selectivity are unknown. However, sex steroid hormone receptor expression in our cell lines was shown only at very low rate, and these hormones failed to influence in vitro proliferation or matrix adhesion. We hypothesize that, instead of a direct action of sex steroids on melanoma cells, their effect is mediated by host factors secondary to hormonal ones. This work was supported by NKFP1a-0024-05.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]