Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/gammac(null) mice: suppression by an inhibitor against NF-kappaB.
We established a novel experimental model for human T-cell leukemia virus type 1 (HTLV-1)-induced tumor using NOD-SCID/gammac(null) (NOG) mice. This model is very useful for investigating the mechanism of tumorigenesis and malignant cell growth of adult T-cell leukemia (ATL)/lymphoma, which still remains unclear. Nine HTLV-1-infected cell lines were inoculated subcutaneously in the postauricular region of NOG mice. As early as 2 to 3 weeks after inoculation, seven cell lines produced a visible tumor while two transformed cell lines failed to do so. Five of seven lines produced a progressively growing large tumor with leukemic infiltration of the cells in various organs that eventually killed the animals. Leukemic cell lines formed soft tumors, whereas some transformed cell lines developed into hemorrhagic hard tumors in NOG mice. One of the leukemic cell lines, ED-40515(-), was unable to produce visible tumors in NOD-SCID mice with a common gamma-chain after 2 weeks. In vivo NF-kappaB DNA binding activity of the ED-40515(-) cell line was higher and the NF-kappaB components were changed compared to cells in vitro. Bay 11-7082, a specific and effective NF-kappaB inhibitor, prevented tumor growth at the sites of the primary region and leukemic infiltration in various organs of NOG mice. This in vivo model of ATL could provide a novel system for use in clarifying the mechanism of growth of HTLV-1-infected cells as well as for the development of new drugs against ATL.
Dewan
M Zahidunnabi
MZ
Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, Japan.
Terashima
Kazuo
K
Taruishi
Midori
M
Hasegawa
Hideki
H
Ito
Mamoru
M
Tanaka
Yuetsu
Y
Mori
Naoki
N
Sata
Tetsutaro
T
Koyanagi
Yoshio
Y
Maeda
Michiyuki
M
Kubuki
Yoko
Y
Okayama
Akihiko
A
Fujii
Masahiro
M
Yamamoto
Naoki
N
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002461:Cell Line, Transformed / Q000637:transplantation*; D004195:Disease Models, Animal; D006085:Graft Survival; D015490:HTLV-I Infections / Q000150:complications; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology / Q000821:virology; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009368:Neoplasm Transplantation / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D009570:Nitriles; D009930:Organic Chemicals; D013450:Sulfones
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000970:Antineoplastic Agents; D016328:NF-kappa B; D009570:Nitriles; D009930:Organic Chemicals; D013450:Sulfones