Sex-dependent liver colonization of human melanoma in SCID mice - Role of host defense mechanisms

J. Dobos, Anita Mohos, J. Tóvári, E. Rásó, Tamás Lorincz, Gergely Zádori, J. Tímár, A. Ladányi

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)497-506
Number of pages10
JournalClinical and Experimental Metastasis
Volume30
Issue number4
DOIs
Publication statusPublished - Apr 2013

Fingerprint

SCID Mice
Defense Mechanisms
Melanoma
Liver
Natural Killer Cells
Kupffer Cells
Survival
Steroid Receptors
Gonadal Steroid Hormones
Efficiency
Cell Line
Antibodies
Neoplasms

Keywords

  • Gender
  • Liver metastasis
  • Melanoma
  • NK cell
  • SCID mice

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sex-dependent liver colonization of human melanoma in SCID mice - Role of host defense mechanisms. / Dobos, J.; Mohos, Anita; Tóvári, J.; Rásó, E.; Lorincz, Tamás; Zádori, Gergely; Tímár, J.; Ladányi, A.

In: Clinical and Experimental Metastasis, Vol. 30, No. 4, 04.2013, p. 497-506.

Research output: Contribution to journalArticle

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