Rapid tumor formation and development of neutrophilia and splenomegaly in nude mice transplanted with human cells expressing human T cell leukemia virus type I or Tax1.
Human T cell leukemia virus type I (HTLV-I) or its transcriptional transactivator, Tax1, was introduced into a human osteosarcoma cell line, HOS, and a Moloney murine sarcoma virus-positive HOS cell line, S+L-HOS. These HTLV-I- or Tax1-expressing cells were injected subcutaneously into nude mice to investigate the effects of HTLV-I on their tumorigenicities. HOS cells did not form any tumors even in the presence of HTLV-I or Tax1. S+L-HOS cells did form small tumors in two-thirds of nude mice. Infection of S+L-HOS cells with HTLV-I, or transduction of Tax1 into S+L-HOS cells markedly facilitated the tumor formation, and the tumor-bearing mice showed marked splenomegaly and neutrophilia. Elevated levels of granulocyte colony-stimulating factor (G-CSF) were detected in sera of these mice and also in the culture supernatants of Tax1-expressing human cells, suggesting that G-CSF in the mouse sera was produced by the human cells. In sera of some mice with splenomegaly and neutrophilia, high levels of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) were observed, suggesting that Tax1 produced by human cells induced mouse cells to produce mGM-CSF. Only S+L-HOS cell lines expressing Tax1 showed high tumorigenicity in nude mice. Thus, this system will be a useful model of tumor formation, splenomegaly and neutrophilia dependent on Tax1.
Soda
Y
Y
Department of Virology and Preventive Medicine, Gunma University School of Medicine, Japan.
Jinno
A
A
Tanaka
Y
Y
Akagi
T
T
Shimotohno
K
K
Hoshino
H
H
D000818:Animals; D017690:Cell Transplantation; D005260:Female; D016356:Gene Products, tax / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006410:Hematopoiesis; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020556:Neutrophil Infiltration; D013163:Splenomegaly / Q000821:virology*; D014407:Tumor Cells, Cultured
D016356:Gene Products, tax; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor