Tumor decellularization reveals proteomic and mechanical characteristics of the extracellular matrix of primary liver cancer

Tienderen, Gilles van; Conboy, James; Muntz, Iain; Willemse, Jorke; Tieleman, Jantine; Monfils, Kathryn; Schurink, Ivo J.; Demmers, Jeroen; Doukas, Michail; Koenderink, Gijsje H.; Laan, Luc J. W. van der; Verstegen, Monique M.A.

doi:10.1016/j.bioadv.2023.213289

Cited by 18 publications

(8 citation statements)

References 82 publications

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“…- Complexity: they require meticulous preparation, involving multiple steps and specialized equipment, which may limit their widespread use. [ 90 ] Scaffold-based microfluidics Cells are cultured within microscale channels that provide a controlled microenvironment for cell growth in a cell-laden scaffold. - Can create precise spatial and temporal control over cell culture conditions (e.g., fluid flow, chemical gradients, and oxygen and nutrient delivery).…”

Section: Scaffold-based Techniques For 3d Cell Culturementioning

confidence: 99%

Scaffold-based 3D cell culture models in cancer research

Abuwatfa,

Pitt,

Husseini

2024

J Biomed Sci

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Three-dimensional (3D) cell cultures have emerged as valuable tools in cancer research, offering significant advantages over traditional two-dimensional (2D) cell culture systems. In 3D cell cultures, cancer cells are grown in an environment that more closely mimics the 3D architecture and complexity of in vivo tumors. This approach has revolutionized cancer research by providing a more accurate representation of the tumor microenvironment (TME) and enabling the study of tumor behavior and response to therapies in a more physiologically relevant context. One of the key benefits of 3D cell culture in cancer research is the ability to recapitulate the complex interactions between cancer cells and their surrounding stroma. Tumors consist not only of cancer cells but also various other cell types, including stromal cells, immune cells, and blood vessels. These models bridge traditional 2D cell cultures and animal models, offering a cost-effective, scalable, and ethical alternative for preclinical research. As the field advances, 3D cell cultures are poised to play a pivotal role in understanding cancer biology and accelerating the development of effective anticancer therapies. This review article highlights the key advantages of 3D cell cultures, progress in the most common scaffold-based culturing techniques, pertinent literature on their applications in cancer research, and the ongoing challenges. Graphical Abstract

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Section: Scaffold-based Techniques For 3d Cell Culturementioning

confidence: 99%

Scaffold-based 3D cell culture models in cancer research

Abuwatfa,

Pitt,

Husseini

2024

J Biomed Sci

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“…The ECM determines the immune environment in cancer to serve as substrate to which immune cells, especially dendritic cells, macrophages and T cells bind and by which they are functionally modulated through, e.g., sensing ECM stiffness via integrin-receptor mediated ECM signals ( 67 – 71 ). Also, HCC shows cancer-specific ECM remodeling with distinct disease-related ECM signatures that exhibit prognostic value ( 72 , 73 ). Moreover, increased ECM stiffness can induce exosome secretion by tumor cells that was shown to promote cancer growth via paracrine Notch signaling, remodeling of the tumor microenvironment ( 74 ) as well as the activation of Yes-associated protein (YAP) and the YAP/TEA domain transcription factor 4 (TEAD4) complex in cancer cells ( 75 , 76 ).…”

Section: Pathophysiology Of Liver Cancermentioning

confidence: 99%

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Casari,

Siegl,

Deppermann

et al. 2023

Front. Immunol.

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During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.

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“…On the other hand, organoids maintain their microenvironment and are better models for drug testing and determining drug response since tumor heterogeneity acts as a main challenge for any therapy [ 41 , 42 ]. van Tienderen et al [ 43 ] recently reported the use of hydrogel which is derived from the extracellular matrix of the tumor to support the maintenance of tumor organoids and established a new pathway for its use as patient-specific medication [ 43 ]. Organoids are more significant than other models like spheroids and sandwich cultures when it comes to monitoring drug toxicity, metabolic activity, or cytoplasmic accumulations they are clinically more relevant.…”

Section: Application Of Organoids For Studying Specific Liver Cancersmentioning

confidence: 99%

Mini-organs with big impact: Organoids in liver cancer studies

BABAR KHAWAR,

WANG,

MAJEED

et al. 2023

Oncology Research

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Hepatocellular carcinoma, the most common primary liver cancer and a leading cause of death, is a difficult disease to treat due to its heterogeneous nature. Traditional models, such as 2D culture and patient-derived xenografts, have not proven effective. However, the development of 3D culture techniques, such as organoids, which can mimic the tumor microenvironment (TME) and preserve heterogeneity and pathophysiological properties of tumor cells, offers new opportunities for treatment and research. Organoids also have the potential for biomarker detection and personalized medication, as well as genome editing using CRISPR/Cas9 to study the behavior of certain genes and therapeutic interventions. This review explores to-the-date development of organoids with a focus on TME modeling in 3D organoid cultures. Further, it discusses gene editing using CRISPR/Cas9 in organoids, the challenges faced, and the prospects in the field of organoids.

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Tumor decellularization reveals proteomic and mechanical characteristics of the extracellular matrix of primary liver cancer

Cited by 18 publications

References 82 publications

Scaffold-based 3D cell culture models in cancer research

Scaffold-based 3D cell culture models in cancer research

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Mini-organs with big impact: Organoids in liver cancer studies

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