American Association for Cancer Research
23266066cir130190-sup-fig5.pdf (121.91 kB)

Supplementary Figure 5 from The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor

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journal contribution
posted on 2023-04-03, 23:11 authored by Agnieszka Swierczak, Andrew D. Cook, Jason C. Lenzo, Christina M. Restall, Judy P. Doherty, Robin L. Anderson, John A. Hamilton

PDF file - 121K, Supplementary Figure 5: 4T1.2 and EMT6.5 tumor cells do not express CSF-1R.



Treatment options are limited for patients with breast cancer presenting with metastatic disease. Targeting of tumor-associated macrophages through the inhibition of colony-stimulating factor-1 receptor (CSF-1R), a key macrophage signaling pathway, has been reported to reduce tumor growth and metastasis, and these treatments are now in clinical trials. Here, we report that, surprisingly, treatment with neutralizing anti–CSF-1R and anti–CSF-1 antibodies, or with two different small-molecule inhibitors of CSF-1R, could actually increase spontaneous metastasis without altering primary tumor growth in mice bearing two independently derived mammary tumors. The blockade of CSF-1R or CSF-1 led to increased levels of serum G-CSF, increased frequency of neutrophils in the primary tumor and in the metastasis-associated lung, as well as increased numbers of neutrophils and Ly6Chi monocytes in the peripheral blood. Neutralizing antibody against the G-CSF receptor, which regulates neutrophil development and function, reduced the enhanced metastasis and neutrophil numbers that resulted from CSF-1R blockade. These results indicate that the role of the CSF-1R/CSF-1 system in breast cancer is far more complex than originally proposed, and requires further investigation as a therapeutic target. Cancer Immunol Res; 2(8); 765–76. ©2014 AACR.