A distinctive biomechanical feature has been identified in the tissues of young patients diagnosed with colorectal cancer, offering potential modern avenues for early detection and treatment of the increasingly prevalent disease. Researchers at the University of Texas at Dallas (UT Dallas) and UT Southwestern Medical Center (UTSW) found that both cancerous and non-cancerous colon tissue in patients under 50 exhibited significantly greater stiffness compared to those of older patients with the same diagnosis.
The findings, published in the January 30 print edition of Advanced Science, suggest that this increased stiffness may create an environment conducive to the development of colorectal cancer in younger individuals. Colorectal cancer incidence typically increases with age, but rates have been rising alarmingly among adults under 50, becoming the leading cause of cancer death for this age group in the United States, according to the American Cancer Society.
“This is the first study to highlight the key role of biomechanical forces in the pathogenesis of early-onset colorectal cancer,” said Dr. Jacopo Ferruzzi, assistant professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science at UT Dallas and a corresponding author of the study. He explained that the research was prompted by clinical observations made by Dr. Emina H. Huang, executive vice chair of research for surgery at UTSW.
“Our team brought an engineering mindset to the table to understand the physical mechanisms involved in early-onset colorectal cancer,” Ferruzzi said.
The colon’s natural flexibility relies on the properties of the extracellular material – a mesh of collagen – within its walls. Yet, this tissue can stiffen when the collagen thickens or becomes abnormally remodeled due to inflammation or fibrosis. Researchers performed biomechanical testing on tissue samples obtained from patients undergoing surgical resection at UTSW. The study included tissue from 19 patients over 50 with average-onset colorectal cancer and 14 patients under 50 diagnosed with early-onset colorectal cancer.
Using a technique called microindentation, the team measured the tissue’s resistance to pressure. These tests, combined with structural and genetic analyses, revealed that tissues from the younger patients were fibrotic and contained more collagen. “We understand from previous studies that cancers are usually stiffer than normal tissues,” Ferruzzi said. “While this was true also in patients with early-onset colorectal cancer, we were surprised to find that both healthy and cancerous tissues from these younger patients were stiffer than those from older patients. This led our team to think that such stiffness could be creating a favorable environment for cancer to develop early in life.”
To investigate this further, the researchers cultured cancer cells on biomaterials mimicking the physical properties of biological tissues. They observed that cancer cells in stiffer environments were more likely to proliferate, indicating that mechanical stiffness promotes more aggressive cancer cell growth. Experiments using patient-derived organoids – miniaturized 3D microtissues that replicate the complexity of the colon – confirmed that a stiff environment accelerates cancer cell growth, regardless of the donor’s age.
Dr. Huang stated, “We consider this study a significant advancement toward identifying those at risk of early-onset colorectal cancer and finding new ways to treat them.”
Ferruzzi expressed hope that the research will lead to improved treatments and prevention strategies for early-onset colorectal cancer. “If we can understand how physical forces fuel colorectal-cancer progression, then we can actually think about early diagnosis and, possibly, therapy,” he said. “More importantly, we can ask the question: How do we stop people from developing cancer that early in life?”
