Prompt tumor formation and maintenance of constitutive NF-kappaB activity of multiple myeloma cells in NOD/SCID/gammacnull mice.
Clinically and biologically relevant animal models are indispensable to evaluate both the pathophysiology and strategies for diagnosis and treatment of multiple myeloma (MM). We examined the tumorigenicity of MM cell lines KMM-1 and U-266 in an in vivo cell proliferation model using NOD/SCID/gammacnull (NOG) mice. Two cell lines were inoculated either subcutaneously (s.c.) in the post-auricular region or intravenously (i.v.) in the tail of NOG mice. The KMM-1 cell line produced a progressively growing large tumor with infiltration of the cells expressing human lambda-chain in various organs of all NOG mice, while the U-266 cell line failed to do so. Tumor cells grown in NOG mice maintained the original histomorphology, as well as expression patterns of tumor markers human lambda Ig light chain and VEGF. Tumor progression in mice also correlated with elevation of serum human soluble IL-6R and gp130. Tumor cells sustained a strong NF-kappaB activity in vivo and induced NF-kappaB components were indistinguishable from those in cells cultured in vitro. The rapid and efficient engraftment of the MM cell line in NOG mice suggests that this is a very useful animal model which could provide a novel system in which to clarify the mechanism of growth of cancer cells, as well as to develop new therapeutic regimens against MM.
Dewan
Md Zahidunnabi
MZ
Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
Watanabe
Mariko
M
Terashima
Kazuo
K
Aoki
Mizuho
M
Sata
Tetsutaro
T
Honda
Mitsuo
M
Ito
Mamoru
M
Yamaoka
Shoji
S
Watanabe
Toshiki
T
Horie
Ryouichi
R
Yamamoto
Naoki
N
D000818:Animals; D002455:Cell Division; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000503:physiopathology* / Q000662:veterinary*; D016328:NF-kappa B / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016328:NF-kappa B