title: Gender difference in bone metastasis of human small cell lung cancer, SBC-5 cells in natural killer-cell depleted severe combined immunodeficient mice.
abstract: Lung cancer frequently develops multiple organ metastases, which thus makes this disease a leading cause of malignancy-related death worldwide. A gender difference is reported to affect the incidence and mortality of lung cancer; however, whether and how the gender difference is involved in lung cancer metastasis is unclear. This study evaluated the gender difference in multiple organ metastases in human small cell lung cancer (SBC-5) cells by using natural killer cell-depleted severe combined immunodeficient mice. Among multiple organ metastases, only bone metastasis formation significantly increased in female mice in comparison to males, while no significant difference was observed in the metastases to the liver and lungs. The suppression of androgen by castration or androgen receptor antagonist treatment in male mice also induced a significant increase of bone metastases. The number of osteoclasts in the bone metastatic lesions was greater in female mice and in mice with androgen suppression than in control male. However, there was no significant difference in the serum concentration of parathyroid hormone-related protein (PTHrP) associated with gender or androgen suppression. An in vitro study also indicated that sex steroid treatment had no effect on the proliferation or PTHrP production in SBC-5 cells. These results indicate that the balance of sex steroids therefore plays an important role in the formation of bone metastasis in small cell lung cancer, and suggests diverse mechanisms of interaction between cancer cells and host cells in the bone microenvironment.
authors.affiliation: Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Gradate School, 3-18-15 Kuramoto-cho Tokushima, Tokushima, 770-8503, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Goto
authors.forename: Masaki
authors.initials: M
authors.lastname: Hanibuchi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Otsuka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ogino
authors.forename: Soji
authors.initials: S
authors.lastname: Kakiuchi
authors.forename: Hisanori
authors.initials: H
authors.lastname: Uehara
authors.forename: Seiji
authors.initials: S
authors.lastname: Yano
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
mesh_terms: D000728:Androgens / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001859:Bone Neoplasms / Q000276:immunology / Q000556:secondary*; D018288:Carcinoma, Small Cell / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009919:Orchiectomy; D044162:Parathyroid Hormone-Related Protein / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
chemical_list: D000728:Androgens; D017931:DNA Primers; D044162:Parathyroid Hormone-Related Protein
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