A novel xenograft model of cutaneous T-cell lymphoma.
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.
Krejsgaard
Thorbjørn
T
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Kopp
Katharina
K
Ralfkiaer
Elisabeth
E
Willumsgaard
Ayelah E
AE
Eriksen
Karsten W
KW
Labuda
Tord
T
Rasmussen
Susanne
S
Mathiesen
Anne-Merete
AM
Geisler
Carsten
C
Lauenborg
Britt
B
Becker
Jürgen C
JC
Zhang
Qian
Q
Wasik
Mariusz A
MA
Odum
Niels
N
Woetmann
Anders
A
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
D015703:Antigens, CD; D006877:Hydroxamic Acids; D019707:Receptors, Chemokine; D000077337:Vorinostat