Brain cancer linked to tissue healing

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 singlecell

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.

https://www.tribuneindia.com/news/health/brain-cancer-linked-to-tissue-healing-194122