Cancer-Associated Fibroblasts Are Key Determinants of Cancer Cell Invasion in the Earliest Stage of Colorectal Cancer

Harryvan, Tom J.; Liao, Chenyi; Danen, Erik H.J.; Spalburg, Vienna N.L.N.; Kiełbasa, Szymon M.; Mei, Hailiang; Goeman, Jelle J.; Jonge-Muller, Eveline S. de; Janson, Stefanus G. T.; Reijden, Johan J. van der; Crobach, Stijn; Hardwick, James C.H.; Boonstra, Jurjen J.; Miranda, Noel F.C.C. de; Hawinkels, Lukas J.A.C.

doi:10.1016/j.jcmgh.2023.04.004

Cited by 11 publications

(4 citation statements)

References 81 publications

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“…The authors suggested that this EMT induction contributed to the chemo-protectant effect seen in their co-culture system [187]. Similar EMT-inducing effects have been seen in other studies where EMT was partially induced in cancer cells by direct co-culturing of CAFs and human CRC tumoroids mimicking either early or late stage CRC [202,203]. Further on, inhibition of WNT signaling in CAFs was shown to induce different CAF subtypes resulting in repression of EMT in CRC tumoroids, highlighting time consuming, and high-throughput methods still have to be improved.…”

Section: Stromal Cellssupporting

confidence: 66%

A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine

Kalla,

Pfneissl,

Mair

et al. 2024

Cell Oncol.

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Cancer is a highly heterogeneous disease, and thus treatment responses vary greatly between patients. To improve therapy efficacy and outcome for cancer patients, more representative and patient-specific preclinical models are needed. Organoids and tumoroids are 3D cell culture models that typically retain the genetic and epigenetic characteristics, as well as the morphology, of their tissue of origin. Thus, they can be used to understand the underlying mechanisms of cancer initiation, progression, and metastasis in a more physiological setting. Additionally, co-culture methods of tumoroids and cancer-associated cells can help to understand the interplay between a tumor and its tumor microenvironment. In recent years, tumoroids have already helped to refine treatments and to identify new targets for cancer therapy. Advanced culturing systems such as chip-based fluidic devices and bioprinting methods in combination with tumoroids have been used for high-throughput applications for personalized medicine. Even though organoid and tumoroid models are complex in vitro systems, validation of results in vivo is still the common practice. Here, we describe how both animal- and human-derived tumoroids have helped to identify novel vulnerabilities for cancer treatment in recent years, and how they are currently used for precision medicine.

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Section: Stromal Cellssupporting

confidence: 66%

A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine

Kalla,

Pfneissl,

Mair

et al. 2024

Cell Oncol.

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“…Similarly, Strating et al co-cultured colon cancer organoids and CAFs in a highly standardized serum-free medium and optimized the ECM to investigate the interaction between cancer cells and CAFs and their effect on immune-related cytokines and T cell proliferation ( Strating et al, 2023 ). In addition, Dang et al studied the contribution of CAFs to the progress of early-stage CRC (T1CRC) through the co-culture model ( Dang et al, 2023 ). Furthermore, Ramos Zapatero et al developed a highly multiplexed mass cytometry platform and found that CAFs can regulate PDO plasticity-shifting proliferative colonic stem cells (proCSCs) to slow-cycling revival colonic stem cells (revCSCs) to protect cancer cells from chemotherapy ( Ramos Zapatero et al, 2023 ).…”

Section: Application Of Organoids In Gi Tumorsmentioning

confidence: 99%

Human patient derived organoids: an emerging precision medicine model for gastrointestinal cancer research

Yan,

He,

Zhu

et al. 2024

Front. Cell Dev. Biol.

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Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality with a poor prognosis. It is one of the leading causes of cancer-related deaths worldwide. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. As a novel preclinical model, tumor patient-derived organoids (PDOs), can be established from patients’ tumor tissue and cultured in the laboratory in 3D architectures. This 3D model can not only highly simulate and preserve key biological characteristics of the source tumor tissue in vitro but also reproduce the in vivo tumor microenvironment through co-culture. Our review provided an overview of the different in vitro models in current tumor research, the derivation of cells in PDO models, and the application of PDO model technology in gastrointestinal cancers, particularly the applications in combination with CRISPR/Cas9 gene editing technology, tumor microenvironment simulation, drug screening, drug development, and personalized medicine. It also elucidates the ethical status quo of organoid research and the current challenges encountered in clinical research, and offers a forward-looking assessment of the potential paths for clinical organoid research advancement.

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“…In a recent work, we showed that already at the earliest stages of CRC (T1-CRC), T1-CAFs can regulate cancer cell invasion and show enhanced ECM remodeling. 9 Moreover, spatial gene expression profiling of T1-CRC lesions showed an increasing predominance of the fibroblast compartment during malignant transformation. 10 Nevertheless, we still have much to learn about how fibroblast composition in the human intestine changes before adenoma formation and whether these changes accelerate or protect against the progression to invasive carcinomas.…”

Section: Caf Origin and Heterogeneitymentioning

confidence: 99%

Fibroblasts in Orchestrating Colorectal Tumorigenesis and Progression

Abudukelimu,

de Miranda,

Hawinkels

2024

Cellular and Molecular Gastroenterology and Hepatology

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Cancer-Associated Fibroblasts Are Key Determinants of Cancer Cell Invasion in the Earliest Stage of Colorectal Cancer

Cited by 11 publications

References 81 publications

A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine

A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine

Human patient derived organoids: an emerging precision medicine model for gastrointestinal cancer research

Fibroblasts in Orchestrating Colorectal Tumorigenesis and Progression

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