TY - JOUR
T1 - A novel xenograft model of cutaneous T-cell lymphoma
AU - Krejsgaard, Thorbjørn
AU - Kopp, Katharina
AU - Ralfkiaer, Elisabeth
AU - Willumsgaard, Ayelah E
AU - Eriksen, Karsten W
AU - Labuda, Tord
AU - Rasmussen, Susanne
AU - Mathiesen, Anne-Merete
AU - Geisler, Carsten
AU - Lauenborg, Britt
AU - Becker, Jürgen C
AU - Zhang, Qian
AU - Wasik, Mariusz A
AU - Odum, Niels
AU - Woetmann, Anders
N1 - Keywords:cutaneous T-cell lymphoma;metastasis;mouse model;mycosis fungoides;vorinostat
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
U2 - 10.1111/j.1600-0625.2010.01138.x
DO - 10.1111/j.1600-0625.2010.01138.x
M3 - Journal article
C2 - 20629733
SN - 0906-6705
VL - 19
SP - 1096
EP - 1102
JO - Experimental Dermatology
JF - Experimental Dermatology
IS - 12
ER -