Blocking the vessel-promoting cytokine M-CSF may be a promising way to fight cancer. Without it, diseased vessels can't grow but healthy ones can, according to Kubota et al. on page 1089.
Many cancer treatments work by disrupting angiogenesis, the formation of new blood vessels that feed growing tumors. Agents that block the angiogenic factor VEGF have shown promise in human clinical trials, but recent studies in mice show that when treatment stops, tumor growth rapidly resumes. Now, Kubota and colleagues find that blocking M-CSF suppresses tumor growth, even after treatment subsides.
Kubota and his team compared the efficacy of M-CSF inhibitors to VEGF inhibitors in a mouse model of osteosarcoma, a bone tumor that expresses high levels of M-CSF. Three weeks of anti-VEGF treatment suppressed tumor growth, but the tumors bounced back when the drug treatment was curtailed. However, tumor growth in mice on a similar regiment of anti–M-CSF remained suppressed in the absence of drug.
Another important distinction between the two inhibitors was the type of vessel growth affected. In mice with injury-induced retinopathy, blocking VEGF inhibited pathological vessel growth but also stunted the recovery of healthy vessels. Blocking M-CSF, on the other hand, impeded only pathological angiogenesis, allowing healthy vessels to recover.
The anti–M-CSF treatment had a lasting effect on pathological angiogenesis, most likely because the extracellular matrix surrounding cancerous vessels was damaged, robbing the tumors of a scaffold on which to grow. And without M-CSF to beckon macrophages responsible for matrix repair, the diseased vessels could not recoup. Meanwhile, the extracellular scaffold of mice treated with anti-VEGF remained intact.
Whether or not other types of cancer rely more on M-CSF, rather than VEGF, for their vascular repairs remains unknown.