Most deaths from breast cancer are due to the onset of metastatic disease, for which there are few curative therapies. A better understanding of molecular mechanisms driving metastasis offers the possibility of improved therapies.

An analysis of plasma from mice bearing mammary tumours revealed that high levels of G-CSF correlated with a more metastatic behavior of the breast tumour.  The high levels of G-CSF mobilised a population of bone marrow derived cells called myeloid derived suppressor cells (MDSC) into the blood and primary tumour. These MDSC were able to suppress the anti-tumour activity of T cells.

Direct injection of G-CSF into mice stimulated the mobilisation of MDSC that were able to suppress CD4⁺/CD8⁺ T cell proliferation, thereby demonstrating their immunosuppressive activity. The injection of G-CSF resulted in an increase in the metastatic capacity of mammary tumours, although no change in the growth of the primary tumours (1).

We tested neutralizing antibodies against the receptors for either CSF-1 (CSF-1R) or G-CSF (G-CSFR) for their ability to suppress breast tumour growth and metastasis in preclinical models. Surprisingly, antibodies against CSF-1R actually promoted metastasis and resulted in an elevation of G-CSF in circulation.

A direct impact of G-CSF signaling on metastasis was demonstrated by showing that treatment of tumour-bearing mice with a neutralising antibody against G-CSFR led to a reduction in MDSC and a reduction in spontaneous metastasis of mammary tumours to lung and bone (2).

Conclusions:These observations offer the possibility of a new therapy for advanced breast cancer based on blockade of G-CSFR signaling. This study raises a question about the use of G-CSF treatment for neutropenia during chemotherapy, although we do not yet know if G-CSF has the same pro-metastatic activity in humans.