Murine mammary carcinoma 4T1 induces a leukemoid reaction with splenomegaly: association with tumor-derived growth factors.

Abstract

A leukemoid reaction with granulocytosis and splenomegaly has been observed in animals and humans with a variety of tumors. We have employed four color flow cytometry to characterize the leukemoid reaction induced by the transplantable mouse mammary carcinoma 4T1 in female BALB/c mice. Gr-1(+) myeloid cells with the morphology of granulocytes increased in peripheral blood from <15% pre-transplant to nearly 80% of total CD45(+) leukocytes at four weeks post-transplant. Though the granulocyte:lymphocyte ratio increased markedly, the absolute numbers of CD19(+) B lymphocytes, CD4(+) and CD8(+) T lymphocytes, and the CD4/CD8 ratio in peripheral blood did not change significantly. Femurs from tumor-bearing mice showed myeloid hyperplasia of the fatty marrow. There was a notable increase in cells with a Gr-1(dim)/CD11b(bright) immature granulocyte phenotype, and these cells were also found in peripheral blood and spleen. Spleen weights had increased 8.5-fold by four weeks post-tumor transplant, mainly due to granulocytic hyperplasia. Cultured 4T1 tumor cells constitutively expressed mRNA for the myeloid colony-stimulating factors G-CSF and GM-CSF, and IFN-gamma-inducible M-CSF transcripts were also detected. Tumors excised from mice had transcripts for G-CSF and GM-CSF, but only G-CSF protein was found in high levels in serum of tumor-bearing mice. These data demonstrate that 4T1 tumor-bearing mice exhibit a leukemoid reaction that apparently is caused by the production of colony-stimulating factors produced by the tumor. The 4T1 tumor may serve as an excellent model for the study of this reaction.

• Authors: Sally A DuPre', Kenneth W Hunter Jr
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 82 Issue 1 Pg. 12-24 (Feb 2007) ISSN: 0014-4800 [Print] Netherlands
• PMID: 16919266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Colony-Stimulating Factors
• Granulocyte Colony-Stimulating Factor
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Bone Marrow (pathology)
• Colony-Stimulating Factors
• Female
• Flow Cytometry
• Granulocyte Colony-Stimulating Factor (blood)
• Granulocyte-Macrophage Colony-Stimulating Factor (blood)
• Granulocytes (pathology)
• Leukemoid Reaction (etiology)
• Lymphocytes (pathology)
• Mammary Neoplasms, Experimental (complications, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Transplantation
• Reverse Transcriptase Polymerase Chain Reaction
• Splenomegaly (etiology)