- Long-term inflammation may stiffen the colon, creating conditions that help early-onset colorectal cancer develop
- In younger patients, tissue was stiffer even in areas that looked healthy, suggesting stiffness may precede cancer
- In lab studies, colorectal cancer cells grew faster in stiffer environments, hinting at new detection and treatment angles
Rates of colorectal cancer in older adults have generally improved over recent decades, but the trend is moving in the wrong direction for younger people.
Early-onset colorectal cancer – cases diagnosed before age 50 – has increased sharply, and the reasons are still being pieced together.
A study led by UT Southwestern, working with colleagues at the University of Texas at Dallas, suggests a biological bridge between chronic inflammation and early-onset colorectal cancer: physical changes in the colon itself.
Specifically, the research points to tissue stiffening as a feature that may help cancer take hold and progress.
The idea is rooted in how long-term inflammation can remodel tissue.
Ongoing inflammation can drive scarring. As scar tissue builds, it changes the architecture of the colon and increases stiffness over time.
Similar processes have been linked to cancer development in other organs, so the researchers asked whether the same might be happening in early-onset colorectal cancer.
They analysed colon tissue from people who underwent surgery to remove colorectal tumours.
Samples included tumour tissue and nearby non-cancerous tissue, allowing direct comparisons between what looks abnormal and what looks healthy.
The key finding was striking: tissue from early-onset colorectal cancer patients was significantly stiffer than tissue from older patients – not only inside tumours but also in surrounding areas that appeared non-cancerous.
That matters because it suggests stiffening might be an early change, happening before a tumour is fully established.
In other words, the colon may become a more permissive environment for cancer, rather than stiffening simply being a consequence of an existing tumour.
To understand why the tissue was stiffer, the team looked closely at collagen, a structural protein that increases and changes during scarring.
In early-onset cases, collagen appeared denser, longer and more aligned – features consistent with more extensive scarring and remodelling.
Gene activity patterns supported the same story, with higher expression of genes linked to collagen metabolism, blood vessel formation and inflammation.
The researchers also explored what this altered environment might do to cancer cells.
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Cells do not just respond to chemical signals – they respond to physical forces too, through a process known as mechanotransduction.
In laboratory experiments, colorectal cancer cells grown on stiffer surfaces multiplied faster and also increased stiffness further, creating a feedback loop.
In three-dimensional models, cancer organoids grew larger and quicker when placed in stiffer surroundings.
If this model holds, it opens two practical doors.
First, measuring intestinal stiffness could potentially help identify people at higher risk, alongside existing screening approaches.
Second, treatments that target mechanotransduction pathways – the systems cells use to sense and respond to stiffness – could become part of future strategies to slow or interrupt cancer development, an approach already being explored in other cancers.
