Samenvatting
This dissertation explores colorectal cancer (CRC) biology, metastasis, tumour heterogeneity,
and therapeutic responses influenced by microbial metabolites. It covers the role of microbial
metabolites in metastasis, the molecular impact of GelE on CRC cells, tumour heterogeneity
in Precision-Cut Tumour Slices (PCCTS), ECM remodelling in PCCTS due to GelE, and
chemotherapy response in this model.
In Chapter 2, a review of bacterial metabolites in CRC metastasis identified GelE, produced
by Enterococcus faecalis, as a potential initiator of early metastasis. This highlights gaps in
our understanding of microbial involvement in CRC progression and suggests future
therapeutic targets.
Chapter 3 examined the effects of GelE on HCT-116 CRC cells, showing how it influences
the cell cycle and mobility, contributing to increased invasiveness. This research addresses
the previously underexplored role of GelE in promoting metastasis.
In Chapter 4, a protocol for culturing PCCTS was developed to study tumour heterogeneity.
The research confirmed the significant variability in CRC tissue and provided strategies to
reduce its impact on experimental results, improving study accuracy.
Chapter 5 extended the analysis of GelE’s effects using the PCCTS model, focusing on ECM
remodelling. The findings highlighted GelE's role in modifying the tumour environment,
further implicating it in metastasis.
In Chapter 6, the PCCTS model was validated by demonstrating its ability to reflect real-
world chemotherapy responses, particularly to FOLFOX-5. The chapter also explored if GelE
influences chemosensitivity.
Overall, this thesis advances CRC research by uncovering the role of GelE in metastasis,
tumour heterogeneity, and chemotherapy response. It addresses key knowledge gaps, such as
GelE's impact on metastasis and CRC cell behaviour. These insights could guide future
personalised cancer treatments and the development of novel therapeutic strategies.
and therapeutic responses influenced by microbial metabolites. It covers the role of microbial
metabolites in metastasis, the molecular impact of GelE on CRC cells, tumour heterogeneity
in Precision-Cut Tumour Slices (PCCTS), ECM remodelling in PCCTS due to GelE, and
chemotherapy response in this model.
In Chapter 2, a review of bacterial metabolites in CRC metastasis identified GelE, produced
by Enterococcus faecalis, as a potential initiator of early metastasis. This highlights gaps in
our understanding of microbial involvement in CRC progression and suggests future
therapeutic targets.
Chapter 3 examined the effects of GelE on HCT-116 CRC cells, showing how it influences
the cell cycle and mobility, contributing to increased invasiveness. This research addresses
the previously underexplored role of GelE in promoting metastasis.
In Chapter 4, a protocol for culturing PCCTS was developed to study tumour heterogeneity.
The research confirmed the significant variability in CRC tissue and provided strategies to
reduce its impact on experimental results, improving study accuracy.
Chapter 5 extended the analysis of GelE’s effects using the PCCTS model, focusing on ECM
remodelling. The findings highlighted GelE's role in modifying the tumour environment,
further implicating it in metastasis.
In Chapter 6, the PCCTS model was validated by demonstrating its ability to reflect real-
world chemotherapy responses, particularly to FOLFOX-5. The chapter also explored if GelE
influences chemosensitivity.
Overall, this thesis advances CRC research by uncovering the role of GelE in metastasis,
tumour heterogeneity, and chemotherapy response. It addresses key knowledge gaps, such as
GelE's impact on metastasis and CRC cell behaviour. These insights could guide future
personalised cancer treatments and the development of novel therapeutic strategies.
| Originele taal-2 | English |
|---|---|
| Kwalificatie | Doctor of Philosophy |
| Toekennende instantie |
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| Begeleider(s)/adviseur |
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| Datum van toekenning | 7-jan.-2025 |
| Plaats van publicatie | [Groningen] |
| Uitgever | |
| DOI's | |
| Status | Published - 2025 |