Mechanisms of tumor-induced neutrophilia: constitutive production of
colony-stimulating factors and their synergistic actions
MY Lee, K Kaushansky, SA Judkins, JL Lottsfeldt, A Waheed and RK Shadduck
Department of Biological Structure, University of Washington School of
Medicine, Seattle 98195.
Transplantation of a murine mammary carcinoma (CE maca) into mice induces
marked granulocytosis and hypercalcemia secondary to excessive bone
resorption. Such responses are not induced by another murine mammary
carcinoma Bc66. In order to understand the mechanisms of these unique
phenomena, we analyzed mRNA of tumor cells for expression of murine
granulopoietic growth factors and studied interactions of tumor- derived
factors using antiserum to a growth factor in vitro and in vivo. The
Northern blot analysis of CE tumor clones revealed the expression of
granulocyte colony stimulating factor (G-CSF) and macrophage colony
stimulating factor (M-CSF), but no other CSF genes, while the Bc66 clone
expressed only M-CSF. The G-CSF and M-CSF gene expression in CE tumor
clones was accompanied by secretion of these proteins in culture. The
granulocyte stimulating activity of CE tumor- derived G-CSF or recombinant
human G-CSF was markedly enhanced by purified M-CSF in vitro. Significant
but variable neutrophilia was observed in mice inoculated with CE tumor
clones. Anti-M-CSF treatment of CE tumor-bearing mice significantly reduced
neutrophilia, but did not affect hypercalcemia. These studies document that
G-CSF and M-CSF are produced constitutively from the CE maca, and G-CSF is
likely responsible for granulocytosis induced by this tumor. G-CSF and
M-CSF function synergistically in granulocyte stimulation in vitro and this
synergism may also play a role in marked granulocytosis of tumor- bearing
animals, providing further evidence of the effect of CSFs in vivo.
Volume 74,
Issue 1,
pp. 115-122,
07/01/1989
Copyright © 1989 by The American Society of Hematology
