Scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) have biofabricated human colorectal cancer miniature organs, called organoids, to better understand how a tumour grows in its natural microenvironment and its response to therapies. This new study is the first to replicate observations of native tumour tissue in a laboratory model and validate it in the context of the whole-body physiology.
Current strategies to understand tumour progression studies are centred on the tumour cells in isolation, but do not capture the interactions between a tumour and its surrounding microenvironment. This leads to inaccuracies in predicting tumour progression and chemotherapy response.
"Tumours are products of their environment. They send signals that can have significant effects on local tissue, and they receive signals from nearby cells and tissues that can alter their progression," said Dr Shay Soker, senior author of the study, ‘Simulating the human colorectal cancer microenvironment in 3D tumor-stroma co-cultures in vitro and in vivo’, published in the journal Scientific Reports.
New technologies that better show the specific properties of a tumour will have a significant effect on patient death rates and lead to development of new treatments which target the cancer, sparing healthy tissue from the side effects of chemotherapy treatments. The WFIRM team previously developed a 3D organoid model of the colon, complete with its unique micro-architecture, and used it to analyse colorectal cancer biopsies to identify significant changes in the miroenvironment.
The team analysed the tumour microenvironment and corresponding ‘finger print’ and found that samples with orderly extracellular matrix - the ‘glue’ that holds cells together - maintained these structures. In contrast, disordered extracellular matrix allowed for a more primitive ‘finger print’. Furthermore, these results were replicated in the context of whole-body physiology, to show for the first time that a pre-structured tumour microenvironment maintains its architecture in the laboratory.
Non-traditional treatments that target the extracellular matrix might provide valuable avenues for developing new treatments or therapies that synergize with existing chemotherapeutic or radiation technologies.
By controlling cancer cell responsiveness through changes to the tumour microenvironment, lower doses of chemotherapy or radiation could become effective, thereby reducing or eliminating many of the undesirable side effects of traditional cancer therapies, as well as yielding lower tumour resistance.
"The 3D bioengineered colon cancer constructs are a promising model for drug development and screening because they can reproduce human physiology at a high level," said Dr Anthony Atala, director of WFIRM.
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