These results may open up prospects for preventing and treating this dangerous type of cancer.
Dr. Emina Huang, professor of surgery in the Department of Colorectal Surgery and executive vice president of surgical research at the University of Texas Southwestern Medical Center, affirmed: "This study is an important step toward identifying people who are most at risk of developing early-onset colorectal cancer and developing new treatment approaches for them."
The University of Texas Southwestern collaborated with researchers from the University of Texas at Dallas to conduct this study. Dr. Jacopo Ferrozzi, Assistant Professor of Bioengineering at the University of Texas at Dallas, explained: "This is the first study to highlight the pivotal role of biomechanical forces in the development of early colorectal cancer, linking connective tissue stiffness to changes in biochemical signaling in cancer cells."
Huang explained that chronic inflammation can lead to tissue scarring and a gradual increase in stiffness, a phenomenon known to promote the growth of certain cancers, such as breast and pancreatic cancer. Therefore, the team investigated whether tissue stiffness might influence the development of early-onset colorectal cancer.
The researchers studied intestinal tissue from patients who had undergone tumor removal surgery: 19 samples from middle-aged colorectal cancer patients (occurring in people over the age of 50) and 14 samples from early-stage colorectal cancer patients (diagnosed in people under the age of 50), including tumors and their healthy margins.
Tests showed that both tumors and healthy tissue were more rigid in samples from patients with early-onset colorectal cancer compared to middle-aged patients, suggesting that increased rigidity may precede cancer development.
To understand the cause of this stiffness, the researchers examined collagen, a protein whose concentration increases and whose shape changes with scarring. They found that collagen in early colorectal cancer samples was denser, longer, more regular, and more mature, confirming the role of scarring.
The researchers also noted a significant increase in the expression of genes associated with collagen metabolism, angiogenesis, and inflammation, which reinforces the hypothesis that scarring resulting from chronic inflammation is responsible for tissue stiffness.
It turns out that early colorectal cancer cells respond to the hardness of their surrounding environment, activating molecular pathways that convert mechanical forces into biochemical signals, which affect their growth and behavior.
Experiments showed that cells grow and multiply more rapidly on more rigid substrates.
Huang said: "The results suggest that a more rigid environment may stimulate the initiation and growth of early colorectal cancer, and that disrupting molecular pathways for mechanical signaling may halt or reverse cancer development."
She added that developing tests to assess bowel stiffness could help identify people who are most at risk of developing early-onset colorectal cancer.
The study was published in the journal Advanced Science.
