Researchers have found that the healing process that follows a brain injury — from trauma to infection and stroke — could spur tumour growth.
“Our data suggest that the right mutational change in particular cells in the brain could be modified by injury to give rise to a tumour,” said Peter Dirks, Professor at the University of Toronto.
The finding, published in the journal Nature Cancer, could lead to a new therapy for glioblastoma patients who currently have limited treatment options with an average lifespan of 15 months after diagnosis, the researchers said.
“Glioblastoma can be thought of as a wound that never stops healing,” Dirks said.
“We’re excited about what this tells us about how cancer originates and grows, and it opens up entirely new ideas about treatment by focusing on the injury and inflammation response,” he added.
The researchers applied the latest single-cell RNA sequencing and Machine Learning (ML) technologies to map the molecular make-up of the glioblastoma stem cells (GSCs), which Dirks’ team previously showed are responsible for tumour initiation and recurrence after treatment.
They found new sub-populations of GSCs that bear the molecular hallmarks of inflammation and which are commingled with other cancer stem cells inside patients’ tumours.
It suggests that some glioblastomas start to form when the normal tissue healing process, which generates new cells to replace those lost to injury, gets derailed by mutations — possibly many years before patients become symptomatic, Dirks said.
Once a mutant cell becomes engaged in wound healing, it cannot stop multiplying because the normal controls are broken and this spurs tumour growth, according to the study.
The team collected GSCs from 26 patients’ tumours and expanded them in the lab to obtain sufficient numbers of the rare cells for analysis. Almost 70,000 cells were analyzed by single-cell RNA sequencing, which detects what genes are switched on in individual cells — an effort led by Laura Richards, a graduate student in Pugh’s lab.
The data confirmed extensive disease heterogeneity, meaning that each tumour contains multiple sub-populations of molecularly distinct cancer stem cells, making recurrence likely as existing therapy is unable to wipe out all the different sub-clones.
A closer look revealed that each tumour has either of the two distinct molecular states – termed “Developmental” and “Injury Response” – or a gradient between the two.
According to the researchers, the developmental state is a hallmark of the glioblastoma stem cells and resembles that of the rapidly dividing stem cells in the brain before birth.
But the second state came as a surprise. The researchers termed it “Injury Response” because it showed an upregulation of immune pathways and inflammation markers such as interferon and TNFalpha, which are indicative of wound healing processes.