Leukaemia cells spread to the brain through a new route reported online in a mouse study in Nature this week. This finding may present new therapeutic opportunities for this fast-moving cancer.
Acute lymphoblastic leukaemia (ALL) often metastasizes to the central nervous system. In contrast to solid tumour brain metastases, ALL is isolated to the leptomeninges, an infrequent invasion site for cancer cells. Although metastasis to the central nervous system is a characteristic across ALL subtypes, a unifying mechanism for this invasion has not yet been determined.
Dorothy Sipkins and colleagues show that ALL cells move along vessels that run between vertebral or calvarial bone marrow and the subarachnoid space. This involves contact between the cancer cells, via integrins expressed on ALL cells, and the basement membrane of these vessels. Interfering with these interactions reduces brain metastasis. Thus, cancer cells have co-opted a route taken during neural migratory pathfinding. The authors suggest that exploring the interactions between normal and malignant immune cells and the vascular pathway may reveal multiple points of intervention to treat the processes that are involved in the invasion of the central nervous system.
The authors also suggest that future studies may reveal whether this unique ALL trafficking route is involved in immune surveillance or inflammatory processes.