title: Sex-dependent liver colonization of human melanoma in SCID mice--role of host defense mechanisms.
abstract: The possibility that endocrine factors may influence the clinical course of malignant melanoma is suggested by the superior survival data of women. In preclinical models we observed a higher rate of colony formation by human melanoma cells in male compared to female SCID mice, but only in the case of the liver and not in other organs. The gender difference could be seen at an early phase of colony formation. On the other hand, in our human melanoma cell lines we failed to detect steroid receptor protein expression, and treatment with sex hormones did not considerably influence their in vitro behavior. Investigating the possible contribution of host cells to the observed gender difference, we performed in vivo blocking experiments applying pretreatment of the animals with Kupffer cell inhibitor gadolinium chloride and the NK cell inhibitor anti-asialo GM1 antibody. While Kupffer cell blockade enhanced melanoma liver colonization equally in the two sexes, a more prominent increase was observed in female than in male mice in the case of NK cell inhibition. Further supporting the importance of NK cells in the lower liver colonization efficiency of melanoma cells in females, gender difference in colony formation was lost in NSG mice lacking NK activity. Although in humans no organ selectivity of gender difference in melanoma progression has been observed according to data in the literature, our results possibly indicate a contribution of natural host defense mechanisms to gender difference in survival of patients with melanoma or other tumor types as well.
authors.affiliation: Department of Surgical and Molecular Pathology, National Institute of Oncology, 7-9. Ráth György u, Budapest 1122, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Dobos
authors.forename: Anita
authors.initials: A
authors.lastname: Mohos
authors.forename: József
authors.initials: J
authors.lastname: Tóvári
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Rásó
authors.forename: Tamás
authors.initials: T
authors.lastname: Lőrincz
authors.forename: Gergely
authors.initials: G
authors.lastname: Zádori
authors.forename: József
authors.initials: J
authors.lastname: Tímár
authors.forename: Andrea
authors.initials: A
authors.lastname: Ladányi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005677:G(M1) Ganglioside / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011987:Receptors, Steroid / Q000378:metabolism; D012737:Sex Factors; D014407:Tumor Cells, Cultured
chemical_list: D012739:Gonadal Steroid Hormones; D011987:Receptors, Steroid; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside