Stress-inducible gene Atf3 dictates a dichotomous macrophage activity in chemotherapy-enhanced lung colonization

Chemotherapy can be a double-edged sword, enhancing cancer progression even while killing cancer cells. This effect is often mediated by stresses on host cells. We found that pre-treatment of mice with cyclophosphamide before cancer cell injection increases the amount of cancer cell colonization of the lung. We determined this effect is at least partially dependent on the stress-inducible gene, Atf3, in monocytes/macrophages. We used microarrays to profile gene expression in WT/KO lung monocytes/macrophages after chemotherapy treatment and intravenous breast cancer cell injection. This was in order to find candidate genes that mediated the colonization-exacerbating role of chemotherapy. WT or Atf3 KO mice were injected with 150 mg/kg cyclophosphamide or vehicle four days before tail-vein injections of 10^6 MVT-1 breast cancer cells. Lungs were collected after 3 days, and monocytes/macrophages were isolated by FACS.