Stimulation of Glioblastoma Proliferation by Macrophages Through CD47/SIRPα

Abstract

Glioblastoma is the most common and aggressive type of adult brain tumour with a need for new treatments. CD47 has been shown to be overexpressed on some human cancers and to interact with macrophages but its role in glioblastoma has not yet been fully explored. Here, we identify a novel role for the CD47/SIRPα interaction between glioblastoma and macrophages in that it can stimulate glioblastoma proliferation in co-cultures. Blocking either CD47 or SIRPα resulted in decreased glioblastoma proliferation. Furthermore, we show that macrophage stimulated glioblastoma proliferation is not occurring through downstream signalling of SIRPα but likely through CD47 to the PI3Kβ pathway. Initial results of co-cultures using glioblastoma cells which express CD47 that is GPI linked to the membrane, and therefore cannot signal downstream, support these findings. The implication of this research is the possibility to develop new therapies targeted at CD47 to decrease glioblastoma proliferation.