TY - JOUR
T1 - A severe combined immunodeficient-hu in vivo mouse model of human primary mantle cell lymphoma
AU - Wang, Michael
AU - Zhang, Liang
AU - Han, Xiaohong
AU - Yang, Jing
AU - Qian, Jianfei
AU - Hong, Sungyoul
AU - Lin, Pei
AU - Shi, Yuankai
AU - Romaguera, Jorge
AU - Kwak, Larry W.
AU - Yi, Qing
PY - 2008/4/1
Y1 - 2008/4/1
N2 - Purpose: To establish a severe combined immunodeficient (SCID)-hu in vivo mouse model of human primary mantle cell lymphoma (MCL) for the study of the biology and novel therapy of human MCL. Experimental Design: Primary MCL cells were isolated from spleen, lymph node, bone marrow aspirates, or peripheral blood of six different patients and injected respectively into human bone chips, which had been s.c. implanted in SCID-hu. Circulating human β2-microglobulin in mouse serumwas used to monitor the engraftment and growth of patient's MCL cells. H & E staining and immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies were used to confirm the tumor growth and migration. Results: Increasing levels of circulating human β2-microglobulin in mouse serum indicated that the patient's MCL cells were engrafted successfully into human bone chip of SCID-hu mice. The engraftment and growth of patient's MCL cells were dependent on human bone marrow microenvironment. Immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies confirmed that patient's MCL cells were able to not only survive and propagate in the bone marrow microenvironment of the human fetal bone chips, but also similar to the human disease, migrate to lymphnodes, spleen, bone marrow, and gastrointestinal tract of hostmice. Treatment of MCL-bearing SCID-hu mice with atiprimod, a novel antitumor compound against the protection of bone marrow stromal cells, induced tumor regression. Conclusion: This is the first human primary MCL animal model that should be useful for the biological and therapeutic research on MCL.
AB - Purpose: To establish a severe combined immunodeficient (SCID)-hu in vivo mouse model of human primary mantle cell lymphoma (MCL) for the study of the biology and novel therapy of human MCL. Experimental Design: Primary MCL cells were isolated from spleen, lymph node, bone marrow aspirates, or peripheral blood of six different patients and injected respectively into human bone chips, which had been s.c. implanted in SCID-hu. Circulating human β2-microglobulin in mouse serumwas used to monitor the engraftment and growth of patient's MCL cells. H & E staining and immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies were used to confirm the tumor growth and migration. Results: Increasing levels of circulating human β2-microglobulin in mouse serum indicated that the patient's MCL cells were engrafted successfully into human bone chip of SCID-hu mice. The engraftment and growth of patient's MCL cells were dependent on human bone marrow microenvironment. Immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies confirmed that patient's MCL cells were able to not only survive and propagate in the bone marrow microenvironment of the human fetal bone chips, but also similar to the human disease, migrate to lymphnodes, spleen, bone marrow, and gastrointestinal tract of hostmice. Treatment of MCL-bearing SCID-hu mice with atiprimod, a novel antitumor compound against the protection of bone marrow stromal cells, induced tumor regression. Conclusion: This is the first human primary MCL animal model that should be useful for the biological and therapeutic research on MCL.
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U2 - 10.1158/1078-0432.CCR-07-4409
DO - 10.1158/1078-0432.CCR-07-4409
M3 - Article
C2 - 18381957
AN - SCOPUS:42249089099
SN - 1078-0432
VL - 14
SP - 2154
EP - 2160
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -