How It Raises Colorectal Cancer Risk in Youth

Younger colorectal cancer patients have stiffer colon tissue that fuels tumor growth, revealing biomechanics as a key factor in early-onset colorectal cancer.

Abnormally stiff colon tissue in younger colorectal cancer patients may promote tumor development, suggesting that biomechanical forces play an important role in early-onset disease (1^✔ ✔Trusted Source
Biomechanical Phenotyping Reveals Unique Mechanobiological Signatures of Early-Onset Colorectal Cancer

Go to source

).
Bioengineers from the University of Texas at Dallas co-led an investigation that identified a distinctive feature in colon tissue obtained from younger individuals with colorectal cancer.

Although colorectal cancer has traditionally been associated with older adults, diagnoses among people younger than 50 have been rising.

Rising Early-Onset Colorectal Cancer and Tissue Stiffness Patterns

The analysis revealed that both tumor tissue and nearby noncancerous colon tissue were mechanically stiffer in younger patients compared with older individuals diagnosed with colorectal cancer.

These observations were published in the journal Advanced Science.

The findings suggest that increased tissue stiffness may create conditions that allow colorectal cancer to develop more easily in people younger than 50. The results may contribute to future strategies for preventing or treating the disease, commonly referred to as early-onset colorectal cancer, which has steadily increased during the past three decades.

Dr. Jacopo Ferruzzi, assistant professor of bioengineering at the Erik Jonsson School of Engineering and Computer Science and a corresponding author, explained that the work is the first to emphasize the critical influence of biomechanical forces in the development of early-onset colorectal cancer.

Rising Cancer Deaths Among Younger Adults

Dr. Emina H. Huang, executive vice chair of research for surgery at UT Southwestern Medical Center and co-corresponding author, described the work as an important step toward identifying individuals who may face a higher risk of early-onset colorectal cancer and discovering improved treatment approaches.

Rates of early-onset colorectal cancer have risen in recent years. Data from the American Cancer Society indicate that the disease has become the leading cause of cancer-related deaths among people younger than 50 in the United States.

Ferruzzi, whose work focuses on biomechanics and mechanobiology, noted that the project began after Huang observed recurring patterns in clinical cases.

Engineering Approach to Physical Mechanisms of Cancer

Ferruzzi explained that the research team applied an engineering perspective to better understand the physical processes involved in early-onset colorectal cancer. His laboratory operates in the Texas Instruments Biomedical Engineering and Sciences Building on the UT Southwestern East Campus.

The facility houses laboratories used by both University of Texas at Dallas and UT Southwestern Medical Center researchers and was designed to promote scientific collaboration between the two institutions.

Colon Structure Changes Linked to Collagen Remodeling

Under normal conditions, the colon functions as a flexible tube that moves waste through the body using coordinated muscle contractions. However, this flexibility can change if the extracellular matrix, a supportive network of collagen within the colon wall, thickens or becomes modified due to inflammation or fibrosis.

To examine this possibility, researchers at the University of Texas at Dallas performed biomechanical tests on tissue samples collected from colorectal cancer patients undergoing surgical tumor removal at UT Southwestern Medical Center.

The investigation included tissue samples from 19 patients older than 50 with typical onset colorectal cancer and 14 patients younger than 50 diagnosed with early-onset colorectal cancer.

Microindentation Testing Reveals Fibrotic Colon Tissue

The team applied microindentation testing, a technique in which a very small probe presses into tissue to determine how strongly it resists pressure. They also assessed how the samples behaved when compressed. Additional structural and genetic analyses further supported the observations.

Results from these combined tests showed that both cancerous and noncancerous colon tissue from younger patients displayed fibrotic features, meaning the tissue appeared scar-like and contained increased levels of collagen. While collagen normally supports tissue structure, excessive accumulation can cause tissues to become unusually rigid.

Ferruzzi noted that earlier investigations have shown cancers are generally stiffer than normal tissues. Although this pattern was also observed in early-onset colorectal cancer, the researchers were surprised to discover that both healthy and cancerous colon tissues in younger patients were stiffer than those found in older individuals. This observation led the team to suspect that such stiffness may create an environment that allows cancer to develop earlier in life.

To explore the potential consequences of stiffness, the researchers cultured cancer cells on biomaterials engineered to replicate the physical characteristics of human tissue. In these experiments, cancer cells placed in stiffer environments multiplied more rapidly, indicating that mechanical rigidity can stimulate more aggressive tumor growth.

Organoid Models Confirm Faster Cancer Cell Growth

The investigators also developed patient-derived organoids, which are small three-dimensional tissue models that replicate many properties of the original organ.

These experiments demonstrated that cancer cells grew more quickly in stiff environments regardless of whether the cells originated from younger or older patients.

Ferruzzi explained that these findings could eventually help scientists design new strategies to prevent or treat early-onset colorectal cancer.

Researchers from the University of Texas at Dallas and UT Southwestern Medical Center conducted the collaborative work at the Texas Instruments Biomedical Engineering and Sciences Building.

Understanding how physical forces drive colorectal cancer progression could help enable earlier diagnosis and lead to new treatment options, while also raising an important question about how to prevent cancer from developing at such an early age.

In conclusion, unusually stiff colon tissue and increased collagen in younger colorectal cancer patients may create conditions that promote tumor growth, offering new insights that could support earlier diagnosis and improved prevention or treatment strategies.

Reference:

1. Biomechanical Phenotyping Reveals Unique Mechanobiological Signatures of Early-Onset Colorectal Cancer – (https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202514693)

Source-Medindia