Australian researchers announced on Mar. 23 the discovery of a new mechanism that drives the growth and spread of glioblastoma, an aggressive form of brain cancer. The study, led by scientists from Adelaide University's Centre for Cancer Biology, identified a previously unrecognised function for the protein CD47 in promoting tumour progression beyond its established role in immune system evasion.
Glioblastoma remains one of the most difficult cancers to treat, with most patients surviving less than 18 months after diagnosis. Current therapies such as surgery, radiation, and chemotherapy have limited effectiveness and are often followed by recurrence.
The research published in PNAS found that CD47 not only helps cancer cells avoid detection by the immune system but also directly assists tumour cells in growing and invading healthy brain tissue. "We've known for some time that CD47 acts as a kind of 'don't eat me' signal that helps cancer cells hide from the immune system," said Dr Nirmal Robinson, senior author of the study. "What we've discovered is that CD47 is doing much more than that; it's actually driving the cancer's ability to spread and grow."
Laboratory experiments showed high levels of CD47 at invasive edges of glioblastoma tumours correlated with poorer patient survival outcomes. In collaboration with Professor Stuart Pitson's team at CCB, researchers demonstrated that removing or blocking CD47 reduced tumour cell proliferation and invasion in both laboratory models and animal studies.
Further investigation revealed a partner protein called ROBO2 working downstream from CD47 to promote tumour growth. The study found that CD47 protects ROBO2 from degradation inside cells by sequestering another protein called ITCH. "Essentially, CD47 is shielding ROBO2, allowing it to accumulate and drive tumour progression," according to Dr Ruhi Polara, who co-led the research with Dr Robinson.
These findings point toward potential new treatment strategies targeting not just immune evasion but also direct molecular pathways within tumours themselves. While current therapies against CD47 have shown limited results in glioblastoma trials so far, disrupting the newly identified pathway may offer more effective options going forward.
"By understanding this mechanism, we now have new targets to explore," Dr Polara said. "This could lead to the development of therapies that specifically block the tumour's ability to spread, which is one of the biggest challenges in treating glioblastoma." Dr Robinson added: "It's not just an immune checkpoint; it's a central regulator of tumour biology in its own right."
