Mimicking Tumor Cell Heterogeneity of Colorectal Cancer in a Patient-derived Organoid-Fibroblast Model

Atanasova, Velina S.; Cardona, Crhistian de Jesus; Hejret, Václav; Tiefenbacher, Andreas; Mair, Theresia; Tran, Loan; Pfneissl, Janette; Draganić, Kristina; Binder, Carina; Kabiljo, Julijan; Clement, Janik; Woeran, Katharina; Neudert, Barbara; Wohlhaupter, Sabrina; Haase, Astrid D.; Domazet, Sandra; Hengstschläger, Markus; Mitterhauser, Markus; Müllauer, Leonhard; Tichý, Boris; Bergmann, Michael; Schweikert, Gabriele; Hartl, Markus; Dolznig, Helmut; Egger, Gerda

doi:10.1016/j.jcmgh.2023.02.014

Cited by 14 publications

(16 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5B that by decreasing the ratio of the cancer cells to fibroblast cells in the primary cell suspension, the tumoroids are shrunk. This size change is attributed to the effect of fibroblast contribution in co-cultured tumoroid formation so that fibroblast cells induce a contractile tension to the multi-cell aggregates within the body of the tumoroids and make that size smaller and maximizing the contact between cells 36,37 . In Fig.…”

Section: Resultsmentioning

confidence: 99%

Tumoroid-on-a-Plate (ToP): Physiologically Relevant Cancer Model Generation and Therapeutic Screening

Seyfoori,

Liu,

Caruncho

et al. 2024

Preprint

View full text Add to dashboard Cite

Employing three-dimensional (3D) in vitro models, including tumor organoids and spheroids, stands pivotal in enhancing cancer therapy. These models bridge the gap between 2D cell cultures and complex in vivo environments, effectively mimicking the intricate cellular interplay and microenvironmental factors found in solid tumors. Consequently, they offer versatile tools for comprehensive studies into cancer progression, drug responses, and tailored therapies. In this study, we present a novel open-surface microfluidic-integrated platform called the Tumoroid-on-a-Plate (ToP) device, designed for generating intricate predictive 3D solid tumor models. By incorporating a tumor mass, stromal cells, and extracellular matrix components, we successfully replicate the complexity of glioblastoma (GBM) and pancreatic adenocarcinoma (PDAC) within our system. Using our advanced ToP model, we were able to successfully screen the effect of various GBM extracellular matrix compositions, such as Collagen and Reelin, on the invasiveness of the GBM cells with the ToP model. The ToP in vitro model also allowed for the screening of chemotherapeutic drugs such as temozolomide and iron-chelators in a single and binary treatment setting on the complex ECM-embedded tumoroids. This helped to investigate the toxic effect of different therapeutics on the viability and apoptosis of our in vitro GBM and PDAC cancer models. Additionally, by co-culturing human-derived fibroblast cells with PDAC tumoroids, the pro-invasive impact of the stromal component of the tumor microenvironment on growth behavior and drug response of the tumoroids was revealed. This study underscores the transformative role of predictive 3D models in deciphering cancer intricacies and highlights the promise of ToP in advancing therapeutic understanding.

show abstract

Section: Resultsmentioning

confidence: 99%

Tumoroid-on-a-Plate (ToP): Physiologically Relevant Cancer Model Generation and Therapeutic Screening

Seyfoori,

Liu,

Caruncho

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Intriguingly, while the immune-reactive TME CAFs promote tumour organoid growth and are associated with lower disease-free survival, the immune-deserted TME CAFs confer chemoprotection to the organoids and are associated with lower overall survival [ 130 ]. Additionally, tumour organoids for CRC [ 131 , 132 ], HCC [ 133 ], and prostate cancer [ 134 ] have all shown a similar trophic effect of CAFs and the conferral of therapeutic resistance, seemingly relying on paracrine signalling. It is noted that patient-derived CAFs rapidly differentiate towards myCAFs in vitro, and thus protocol optimisation is key in preserving the CAF phenotype in organoids [ 132 ].…”

Section: Translational Immuno-oncology Research With Organoidsmentioning

confidence: 99%

“…Additionally, tumour organoids for CRC [ 131 , 132 ], HCC [ 133 ], and prostate cancer [ 134 ] have all shown a similar trophic effect of CAFs and the conferral of therapeutic resistance, seemingly relying on paracrine signalling. It is noted that patient-derived CAFs rapidly differentiate towards myCAFs in vitro, and thus protocol optimisation is key in preserving the CAF phenotype in organoids [ 132 ]. Investigation into the recruitment and reprogramming of CAFs, and their paracrine effect on tumour cells and immune cells, will yield exciting insight into the immunoregulatory functions of CAFs and offer new therapeutic opportunities, which are discussed next.…”

Section: Translational Immuno-oncology Research With Organoidsmentioning

confidence: 99%

Organoids as an Enabler of Precision Immuno-Oncology

Zhao

Fong

Seow

et al. 2023

Cells

View full text Add to dashboard Cite

Since the dawn of the past century, landmark discoveries in cell-mediated immunity have led to a greater understanding of the innate and adaptive immune systems and revolutionised the treatment of countless diseases, including cancer. Today, precision immuno-oncology (I/O) involves not only targeting immune checkpoints that inhibit T-cell immunity but also harnessing immune cell therapies. The limited efficacy in some cancers results mainly from a complex tumour microenvironment (TME) that, in addition to adaptive immune cells, comprises innate myeloid and lymphoid cells, cancer-associated fibroblasts, and the tumour vasculature that contribute towards immune evasion. As the complexity of TME has called for more sophisticated human-based tumour models, organoids have allowed the dynamic study of spatiotemporal interactions between tumour cells and individual TME cell types. Here, we discuss how organoids can study the TME across cancers and how these features may improve precision I/O. We outline the approaches to preserve or recapitulate the TME in tumour organoids and discuss their potential, advantages, and limitations. We will discuss future directions of organoid research in understanding cancer immunology in-depth and identifying novel I/O targets and treatment strategies.

show abstract

“…13 In the former approach, both cell types are combined at a desired ratio and embedded in an extracellular matrix (ECM), such as Matrigel or collagen gel, to support cells in a complex 3D architecture that closely mimics the original tumor microenvironment. 6,[14][15][16] This method offers the advantage of precise control of over heterotypic and homotypic interactions, allowing for both physical contact and interactions through soluble factors. On the other hand, paracrine co-culture methods involve using membrane inserts to physically separate the co-cultured cells, enabling the study of cell signaling interactions between fibroblasts and tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Deciphering fibroblast-induced drug resistance in non-small cell lung carcinoma through patient-derived organoids in agarose microwells

Luan,

Pulido,

Isagirre

et al. 2024

Lab Chip

View full text Add to dashboard Cite

show abstract

Mimicking Tumor Cell Heterogeneity of Colorectal Cancer in a Patient-derived Organoid-Fibroblast Model

Cited by 14 publications

References 114 publications

Tumoroid-on-a-Plate (ToP): Physiologically Relevant Cancer Model Generation and Therapeutic Screening

Tumoroid-on-a-Plate (ToP): Physiologically Relevant Cancer Model Generation and Therapeutic Screening

Organoids as an Enabler of Precision Immuno-Oncology

Deciphering fibroblast-induced drug resistance in non-small cell lung carcinoma through patient-derived organoids in agarose microwells

Contact Info

Product

Resources

About