title: Human melanoma metastasis in NSG mice correlates with clinical outcome in patients.
abstract: Studies of human cancer metastasis have been limited by a lack of experimental assays in which cancer cells from patients metastasize in vivo in a way that correlates with clinical outcome. This makes it impossible to study intrinsic differences in the metastatic properties of cancers from different patients. We recently developed an assay in which human melanomas readily engraft in nonobese diabetic/severe combined immunodeficient interleukin-2 receptor-γ chain null (NSG) mice. We show that melanomas from 25 patients exhibited reproducible differences in the rate of spontaneous metastasis after transplantation into NSG mice and that these differences correlated with clinical outcome in the patients. Stage IIIB/C melanomas that formed distant metastases within 22 months in patients also formed tumors that metastasized widely in NSG mice, whereas stage IIIB/C melanomas that did not form distant metastases within 22 to 50 months in patients metastasized more slowly in NSG mice. These differences in the efficiency of metastasis correlated with the presence of circulating melanoma cells in the blood of NSG mice, suggesting that the rate of entry into the blood is one factor that limits the rate of metastasis. The study of NSG mice can therefore yield information about the metastasis of human melanomas in vivo, in this case revealing intrinsic differences among stage III melanomas in their ability to circulate/survive in the blood and to metastasize.
authors.affiliation: Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA.
authors.forename: Elsa
authors.initials: E
authors.lastname: Quintana
authors.forename: Elena
authors.initials: E
authors.lastname: Piskounova
authors.forename: Mark
authors.initials: M
authors.lastname: Shackleton
authors.forename: Daniel
authors.initials: D
authors.lastname: Weinberg
authors.forename: Ugur
authors.initials: U
authors.lastname: Eskiocak
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Fullen
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Johnson
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency* / Q000378:metabolism; D008163:Luminescent Measurements; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D012878:Skin Neoplasms / Q000473:pathology*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D053631:Interleukin Receptor Common gamma Subunit