Ehrlich tumor stimulates extramedullar hematopoiesis in mice without secreting identifiable colony-stimulating factors and without engagement of host T cells.
Tumor growth is associated with neutrophilia, thrombocytosis, and extramedullar hematopoiesis. The mechanism(s) accounting for these phenomena is unclear, although granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or granulocyte colony-stimulating factor (G-CSF) released by tumor cells have been involved. We studied whether CSF released by Ehrlich tumor (ET) may play a role. A comparative study was performed with two cell variants (ET and ET/0) growing in euthymic, nude, and SCID mice. Extramedullar hematopoiesis was assessed in the spleen by scoring organ enlargement, wheat germ agglutinin ve+ cells, and interleukin 3-dependent granulocyte-macrophage colony-forming unit (GM-CFU). Both cell lines showed the same cytokine profile by reverse transcriptase polymerase chain reaction, including GM-CSF, G-CSF, and macrophage colony-stimulating factor (M-CSF); yet, only ET cells produced detectable colony-stimulating activity in vitro, mainly due to GM-CSF. No differences in tumorigenicity were noted between ET and ET/0 cells inoculated to normal or immunodeficient mice. An increase in extramedullar hematopoiesis, accompanied by neutrophilia and thrombocytosis, was associated with tumor progression irrespective of the cell line. A strong correlation was obtained between the increase in splenic GM-CFU and tumor mass (r = 0.96, p < 0.0001) that was independent on the tumor cell line, strain of mice, or stage of tumor development. The results point against CSF released by tumor cells and/or reactive host T cells as the only factors involved in the extramedullar hematopoiesis in this tumor model. The remarkable correlation between splenic GM-CFU and the tumor mass still suggests that a factor(s) of tumor origin may play a critical role.
Ruiz de Morales
J
J
Department of Immunology, Hospital Clínico San Carlos, Madrid, Spain.
Vélez
D
D
Subiza
J L
JL
D000818:Animals; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006411:Hematopoiesis, Extramedullary; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000502:physiology*
D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor