Rising Rates of Early-Onset Colorectal Cancer Linked to Tissue Stiffness

A new study from the University of Texas at Dallas (UT Dallas) and UT Southwestern Medical Center (UTSW) has identified a key biomechanical difference in the colon tissue of younger patients diagnosed with colorectal cancer. Researchers found that both cancerous and non-cancerous tissue in individuals under 50 is significantly stiffer than in older patients with the same disease, potentially creating an environment that promotes earlier cancer development. This research offers new avenues for understanding and addressing the alarming rise in early-onset colorectal cancer (EO CRC).

The Rise of Early-Onset Colorectal Cancer

Colorectal cancer is traditionally a disease associated with older adults. However, over the past three decades, there has been a concerning increase in diagnoses among younger individuals. According to the American Cancer Society, it is now the leading cause of cancer death for people younger than 50 in the United States. This shift has prompted researchers to investigate the unique biological factors driving this trend.

Stiffness as a Key Factor

The UT Dallas study, published in Advanced Science, focused on the physical properties of colon tissue. Researchers performed biomechanical testing, including microindentation, on samples collected from 19 patients over 50 with average-onset colorectal cancer and 14 patients under 50 with early-onset colorectal cancer undergoing surgical resection at UTSW. The results revealed that the tissue from younger patients exhibited increased stiffness, even in areas without cancerous cells.

“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 at UT Dallas and a corresponding author of the study. “We consider this study a significant advancement toward identifying those at risk of early-onset colorectal cancer and finding new ways to treat them,” added Dr. Emina H. Huang, executive vice chair of research for surgery at UTSW and co-corresponding author.

How Stiffness Impacts Cancer Development

The researchers believe that increased stiffness is linked to changes in the extracellular matrix – the network of collagen and other molecules that provide structural support to tissues. In younger patients, this matrix appears to be abnormally remodeled, leading to fibrosis (scar-like tissue) and increased collagen deposition. This stiffer environment can then influence cancer cell behavior.

To investigate this further, the team conducted experiments culturing cancer cells on biomaterials mimicking the stiffness of different tissues. They found that cancer cells grew and proliferated more aggressively in the stiffer environments, demonstrating a direct link between mechanical stiffness and cancer progression. Experiments using patient-derived organoids – miniature 3D models of the colon – confirmed these findings, showing that stiffness accelerates cancer cell growth regardless of the patient’s age.

Implications for Prevention and Treatment

Understanding the role of tissue stiffness in EO CRC opens up new possibilities for prevention and treatment. Dr. Ferruzzi suggests that future research could focus on identifying individuals at higher risk based on biomechanical markers and developing therapies that target the physical microenvironment of the colon.

“If we can understand how physical forces fuel colorectal-cancer progression, then we can actually think about early diagnosis and, possibly, therapy,” Dr. Ferruzzi explained. “More importantly, we can ask the question: How do we stop people from developing cancer that early in life?”

Key Takeaways

• Early-onset colorectal cancer is increasing in prevalence, becoming the leading cause of cancer death for adults under 50.
• A new study reveals that colon tissue is significantly stiffer in younger patients with colorectal cancer, even in non-cancerous areas.
• Increased stiffness is linked to changes in the extracellular matrix and increased collagen deposition.
• Stiffer environments promote cancer cell growth and proliferation.
• This research suggests new avenues for early diagnosis, prevention, and treatment of early-onset colorectal cancer.