Autonomous production of granulocyte-colony stimulating factor in tumour xenografts associated with leukocytosis.
Leukocytosis sometimes accompanies malignant neoplasms in the absence of infection. It is thought that the production of colony-stimulating factor by neoplasms is the most potent cause of tumour-induced leukocytosis; several mechanisms have been suggested to explain this. We examined 155 human tumour xenografts established in nude mice, and found that 17 of the xenografts induced remarkable leukocytosis (> 15,000 microliters-1) in nude rats. We examined granulocyte colony-stimulating factor (G-CSF) production by the xenografts to study the mechanisms underlying this tumour-induced leukocytosis. Ten of the 17 xenografted human tumours appeared to express the G-CSF gene. Serum G-CSF increased, to concentrations of 179-37,218 pg ml-1, in host animals transplanted with the ten xenografts expressing the G-CSF gene transcripts. The biological activity of serum G-CSF also increased, to concentrations of 206-9,074 pg ml-1, in the host animals transplanted with the ten xenografts. Immunohistochemical analysis demonstrated G-CSF production at the cellular level in three of the ten xenografts. These results suggested that the production of G-CSF is a common event in human tumour xenografts associated with leukocytosis, but that factors other than G-CSF are also likely to be involved. Leukocytosis induced by neoplasms seems to be a heterogeneous and complex disorder.
Katoh
Y
Y
Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
Nakamura
M
M
Ohnishi
Y
Y
Shimamura
K
K
Ueyama
Y
Y
Tamaoki
N
N
D000818:Animals; D015152:Blotting, Northern; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007958:Leukocyte Count; D007964:Leukocytosis / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016179:Granulocyte Colony-Stimulating Factor