title: A novel xenograft model of cutaneous T-cell lymphoma.
abstract: Cutaneous T-cell lymphomas (CTCLs) are characterized by accumulation of malignant T cells in the skin. Early disease resembles benign skin disorders but during disease progression cutaneous tumors develop, and eventually the malignant T cells can spread to lymph nodes and internal organs. However, because of the lack of suitable animal models, little is known about the mechanisms driving CTCL development and progression in vivo. Here, we describe a novel xenograft model of tumor stage CTCL, where malignant T cells (MyLa2059) are transplanted to NOD/SCID-B2m(-/-) (NOD.Cg-Prkdc(scid) B2m(tm1Unc) /J) mice. Subcutaneous transplantation of the malignant T cells led to rapid tumor formation in 43 of 48 transplantations, whereas transplantation of non-malignant T cells isolated from the same donor did not result in tumor development. Importantly, the tumor growth was significantly suppressed in mice treated with vorinostat when compared to mice treated with vehicle. Furthermore, in most mice the tumors displayed subcutaneous and/or lymphatic dissemination. Histological, immunohistochemical and flow cytometric analyses confirmed that both tumors at the inoculation site, as well as distant subcutaneous and lymphatic tumors, originated from the transplanted malignant T cells. In conclusion, we describe a novel mouse model of tumor stage CTCL for future studies of disease dissemination and preclinical evaluations of new therapeutic strategies.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.forename: Katharina
authors.initials: K
authors.lastname: Kopp
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiaer
authors.forename: Ayelah E
authors.initials: AE
authors.lastname: Willumsgaard
authors.forename: Karsten W
authors.initials: KW
authors.lastname: Eriksen
authors.forename: Tord
authors.initials: T
authors.lastname: Labuda
authors.forename: Susanne
authors.initials: S
authors.lastname: Rasmussen
authors.forename: Anne-Merete
authors.initials: AM
authors.lastname: Mathiesen
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.forename: Britt
authors.initials: B
authors.lastname: Lauenborg
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use; D016130:Immunophenotyping; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000473:pathology; D019707:Receptors, Chemokine / Q000378:metabolism; D015203:Reproducibility of Results; D012867:Skin / Q000473:pathology; D014183:Transplantation, Heterologous / Q000473:pathology*; D000077337:Vorinostat
chemical_list: D015703:Antigens, CD; D006877:Hydroxamic Acids; D019707:Receptors, Chemokine; D000077337:Vorinostat