The tumour vasculature is known to have tumour-promoting effects, such as increased tumour growth and invasion. Rafii and colleagues now show that tumour endothelial cells participate in an intricate crosstalk with lymphoma cells to promote lymphoma cell invasiveness and resistance to chemotherapy (Cancer Cell 25, 350–365; 2014).

The authors devised an endothelial and lymphoma cell co-culture system followed by in vivo mouse experiments and transcriptomic profiling to demonstrate that endothelial cells promote expansion of an aggressive and chemoresistant lymphoma cell subpopulation. A series of elegant in vitro and in vivo experiments demonstrated that FGF4 produced by B cell lymphoma cells activated FGFR1 signalling in endothelial cells, leading to the upregulation of the Notch ligand Jag1. Endothelial cells expressing Jag-1 were in turn shown to activate Notch2 signalling in neighbouring lymphoma cells to drive their expansion, lymphomagenesis, extranodal invasiveness and resistance to chemotherapy, as shown using an Eμ-Myc lymphoma mouse model. Disrupting the crosstalk of endothelial and lymphoma cells by genetic inactivation of Fgfr1 or Jag1 in endothelial cells reduced tumour growth and increased mouse survival and sensitivity to chemotherapeutic agents.

These findings elucidate a non-cell-autonomous mechanism through which lymphoma cells foster their own expansion and aggressiveness, by instigating the formation of a pro-tumorigenic vascular niche.