New research, led by experts at the University of Nottingham, has revealed how collagen in the tumour environment can alter bowel cancer cell behaviour and influence inflammatory responses to chemotherapy, highlighting potential new avenues for future research into cancer treatment.
The findings, published the Journal of Experimental & Clinical Cancer Research, highlight the importance of the environment surrounding cancer cells in shaping how they behave and respond to treatment.
The study was led by Dr Paloma Ordóñez-Morán from the University of Nottingham's School of Medicine This four-year project was undertaken as a PhD project by student Samna Sagadevan through the Medical Research Council iCASE programme. It was a collaborative team effort, made possible by close partnerships between researchers, pathologists, nurses, gastroenterologists and surgeons whose contributions were essential to the project's success.
Bowel cancer, also known as colorectal cancer, develops within a complex tumour environment. Proteins such as collagen, which provides structural support to tissues, can influence how cancer cells behave. However, how these interactions affect cancer progression and responses to chemotherapy remains only moderately understood.
To investigate this, researchers grew mini-tumours, known as patient-derived organoids (PDOs), from colorectal cancer tissue donated by patients in Nottingham. These organoids allowed the team to study cancer cell behaviour in the laboratory while retaining important features of the original tumours.
The researchers exposed the organoids to collagen, a structural protein found in the tissue surrounding tumours, to recreate aspects of the tumour environment. They then used laboratory techniques to examine changes in cell characteristics, gene activity and biological signalling, investigating how collagen influenced cancer cell behaviour and responses to treatment.
By comparing cancer organoids under different conditions, we investigated how the surrounding environment can influence the way cancer cells behave and respond to chemotherapy. This approach helps us understand why tumours may respond differently to the same treatment and could ultimately contribute to developing more personalised cancer treatments."
The team found that a collagen-rich environment activated signalling pathways associated with changes in cancer cell behaviour, increased production of a protein called LTBP2, and promoted features of epithelial–mesenchymal transition (EMT). EMT is a process in which cells acquire characteristics associated with increased mobility and changes in how they interact with surrounding tissues, and it has been linked to cancer progression.
The study also found that exposure to type I collagen enhanced inflammatory responses following chemotherapy. This suggests that interactions between cancer cells and their surrounding tissue may influence how tumours respond to treatment.
Understanding these interactions could help researchers identify new approaches to studying and potentially improving colorectal cancer treatment. Further research is needed to determine whether targeting the pathways identified in this study could safely and effectively improve outcomes for patients.
Working with organoids grown from tissue donated by patients meant every experiment felt connected to a real person. Seeing how much the surrounding environment changed the way the same cancer cells behaved and responded to chemotherapy was striking, and it reinforced why understanding each patient's tumour in context matters for developing better interventions."
