Heterocellular 3D scaffolds as biomimetic to recapitulate the tumor microenvironment of peritoneal metastases in vitro and in vivo

Jaeghere, Emiel De; Vlieghere, Elly De; Hoorick, Jasper Van; Vlierberghe, Sandra Van; Wagemans, Glenn; Pieters, Leen; Melsens, Elodie; Praet, Marleen; Dorpe, Jo Van; Boone, Matthieu; Ghobeira, Rouba; Bracke, Marc; Vanhove, Christian; Neyt, Sara; Berx, Geert; Geest, Bruno G. De; Dubruel, Peter; Declercq, Heidi; Ceelen, Wim; Wever, Olivier De

doi:10.1016/j.biomaterials.2017.12.017

Cited by 35 publications

(37 citation statements)

References 36 publications

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“…There are many different 3D assays described in the literature or available commercially (Kimlin et al, 2013b ; Hoarau-Véchot et al, 2018 ), in the context of CRC (Nietzer et al, 2016 ; Pereira et al, 2016 ), vasculature modeling (Bersini et al, 2016 ; Haase and Kamm, 2017 ) and cancer invasion (Berens et al, 2015 ; De Jaeghere et al, 2018 ). The model that we proposed has been specifically developed to study the effect of cells of the TME, and in particular fibroblasts, on tumor cell motility and invasion.…”

Section: Discussionmentioning

confidence: 99%

Characterization and In Vivo Validation of a Three-Dimensional Multi-Cellular Culture Model to Study Heterotypic Interactions in Colorectal Cancer Cell Growth, Invasion and Metastasis

Cattin

Ramont²,

Rüegg

2018

Front. Bioeng. Biotechnol.

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Colorectal cancer (CRC) is the third cause of cancer-related mortality in industrialized countries. Local invasion and metastasis formation are events associated with poor prognosis for which today there are no effective therapeutic options. Invasion and metastasis are strongly modulated by cells of the tumor microenvironment (TME), in particular fibroblasts and endothelial cells. Unraveling interactions between tumor cells and cells of the TME may identify novel mechanisms and therapeutic targets to prevent or treat metastasis. We report here the development and in vivo validation of a 3D tumor spheroid model to study the interactions between CRC cells, fibroblasts and endothelial cells in vitro. Co-cultured fibroblasts promoted SW620 and HCT116 CRC spheroid invasion, and this was prevented by the SRC and FGFR kinase inhibitors Dasatinib and Erdafitinib, respectively. To validate these findings in vivo, we injected SW620 cells alone or together with fibroblasts orthotopically in the caecum of mice. Co-injection with fibroblasts promoted lung metastasis growth, which was fully reversed by treatment with Dasatinib or Erdafitinib. Co-culture of SW620 or HCT116 CRC spheroids with endothelial cells suppressed spheroid growth while it had no effect on cancer cell migration or invasion. Consistent with this in vitro effect, co-injected endothelial cells significantly inhibited primary tumor growth in vivo. From these experiments we conclude that effects on cancer cell invasion and growth induced by co-cultured TME cells and drug treatment in the 3D spheroid model in vitro, are predictive of in vivo effects. The 3D spheroid model may be considered as an attractive model to study the effect of heterotypic cellular interactions and drug activities on cancer cells, as animal testing alternative. This model may be adapted and further developed to include different types of cancer and host cells and to investigate additional functions and drugs.

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Section: Discussionmentioning

confidence: 99%

Characterization and In Vivo Validation of a Three-Dimensional Multi-Cellular Culture Model to Study Heterotypic Interactions in Colorectal Cancer Cell Growth, Invasion and Metastasis

Cattin

Ramont²,

Rüegg

2018

Front. Bioeng. Biotechnol.

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“…Several studies have used these scaffolds to make an ex vivo tumor recapitulating the complexity of the tumor microenvironment. This has been achieved by including cancer cells, immune cells, fibroblasts, growth factors, and stromal components [86][87][88]. In PCa, this methodology has been used for the development of high-complexity bona fide peritoneal implants, although it is debatable whether this should be defined as an in vivo model per se.…”

Section: D-biomimetics Peritoneal Implantsmentioning

confidence: 99%

“…Peritoneal implants present a complex structure, and the challenge of 3D culture is to mimic these ex vivo as realistically as possible so as to improve engraftment and the clinical biology in animal models. In order to achieve this, Emiel De Jaeghere et al took into account the heterocellularity of 3D scaffolds in order to generate scaffolds which could then be implanted in the peritoneal cavity more successfully [86]. For that purpose, this group used polylactic acid (PLA) scaffolds with collagen type I hydrogel, co-seeding SKOV-3 cells (ovarian cancer), and cancer-associated fibroblasts (CAFs) not only to enhance the paracrine factor to improve spheroid formation in vitro, but also to enhance cancer cell survival, and angiogenesis.…”

Section: D-biomimetics Peritoneal Implantsmentioning

confidence: 99%

“…In fact, it was observed that CAFs, endothelial cells, macrophages, and cancer cells showed similar features when compared with patient-derived peritoneal metastasis. The authors concluded that this scaffold model represents a promising platform for the preclinical study of drug penetration and efficacy following delivery of intraperitoneal chemotherapy, among other therapeutic agents [86].…”

Section: D-biomimetics Peritoneal Implantsmentioning

confidence: 99%

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Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications

Bella

Trani

Fernandez‐Sendin

et al. 2021

Cancers

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Peritoneal carcinomatosis of primary tumors originating in gastrointestinal (e.g., colorectal cancer, gastric cancer) or gynecologic (e.g., ovarian cancer) malignancies is a widespread type of tumor dissemination in the peritoneal cavity for which few therapeutic options are available. Therefore, reliable preclinical models are crucial for research and development of efficacious treatments for this condition. To date, a number of animal models have attempted to reproduce as accurately as possible the complexity of the tumor microenvironment of human peritoneal carcinomatosis. These include: Syngeneic tumor cell lines, human xenografts, patient-derived xenografts, genetically induced tumors, and 3D scaffold biomimetics. Each experimental model has its own strengths and limitations, all of which can influence the subsequent translational results concerning anticancer and immunomodulatory drugs under exploration. This review highlights the current status of peritoneal carcinomatosis mouse models for preclinical development of anticancer drugs or immunotherapeutic agents.

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“…In the transparent poly ( l ‐lactic acid) scaffolds with controlled pore size, geometry and surface properties, cancer‐associated fibroblasts (CAF), endothelial cells, macrophages and cancer cells form the multifaceted cell–cell and cell–ECM interactions in complex tissue‐engineering tumor models, [ 190 ] which show spatial and quantitative aspects as similarly observed in patient‐derived peritoneal metastases. The biomimetic synthetic scaffolds provide an advanced technology platform for both in vitro and in vivo experiments of the peritoneal metastasis and facilitate cancer cells and other cells to crosstalk with their niche via tissue‐specific pathways.…”

Section: Instructive Cell Constructs In Tissue Engineering and Precismentioning

confidence: 99%

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

Yang

Zhao

2020

Advanced Science

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mouse intestinal stem cells and primary colorectal cancer cells can be propagated in vitro long term, [1] there is an urgent need to develop more physiologically relevant, efficient, and robust precise oncology models that closely recapitulate the genetic and morphological heterogeneous composition and mimic the arrangement pattern of cancer cells in the original tumor. [2] To our knowledge in biomedical research, hydrogel is the best tool to reconstruct precise oncology models in vitro, especially tumor organoid, which not only recapitulates in vivo biology and microenvironmental factors, but also at large extent allows side-by-side comparison to evaluate the translational potential of 3D model systems to the patients. [2a,3] Generally, hydrogels are mainly composed of hydrophilic polymeric scaffolds that absorb large amounts of water, so the hydrogel matrix better mimics elastic and viscoelastic properties in ECM and microscale topographies of cell matrices, which controls proper cell morphology, directs viable cell behaviors, and drives in vivo fundamental cell-cell or cell-ECM interactions. [4] To recapitulate pathophysiological features of human tumors and imitate various aspects of human tumorigenesis in vivo, hydrogels can provide a realistic platform to establish a useful bridge between in vitro assays and in vivo cell microenvironments. In current biomedical applications, there are many kinds of hydrogels to be developed to mimic the biological properties of ECM, such Designer self-assembling peptides form the entangled nanofiber networks in hydrogels by ionic-complementary self-assembly. This type of hydrogel has realistic biological and physiochemical properties to serve as biomimetic extracellular matrix (ECM) for biomedical applications. The advantages and benefits are distinct from natural hydrogels and other synthetic or semisynthetic hydrogels. Designer peptides provide diverse alternatives of main building blocks to form various functional nanostructures. The entangled nanofiber networks permit essential compositional complexity and heterogeneity of engineering cell microenvironments in comparison with other hydrogels, which may reconstruct the tumor microenvironments (TMEs) in 3D cell cultures and tissue-specific modeling in vitro. Either ovarian cancer progression or recurrence and relapse are involved in the multifaceted TMEs in addition to mesothelial cells, fibroblasts, endothelial cells, pericytes, immune cells, adipocytes, and the ECM. Based on the progress in common hydrogel products, this work focuses on the diverse designer self-assembling peptide hydrogels for instructive cell constructs in tissue-specific modeling and the precise oncology remodeling for ovarian cancer, which are issued by several research aspects in a 3D context. The advantages and significance of designer peptide hydrogels are discussed, and some common approaches and coming challenges are also addressed in current complex tumor diseases.

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Heterocellular 3D scaffolds as biomimetic to recapitulate the tumor microenvironment of peritoneal metastases in vitro and in vivo

Cited by 35 publications

References 36 publications

Characterization and In Vivo Validation of a Three-Dimensional Multi-Cellular Culture Model to Study Heterotypic Interactions in Colorectal Cancer Cell Growth, Invasion and Metastasis

Characterization and In Vivo Validation of a Three-Dimensional Multi-Cellular Culture Model to Study Heterotypic Interactions in Colorectal Cancer Cell Growth, Invasion and Metastasis

Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

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