Biophysics Role and Biomimetic Culture Systems of ECM Stiffness in Cancer EMT

Tian, Hao; Shi, Hanhan; Yu, Jie; Ge, Shengfang; Ruan, Jing

doi:10.1002/gch2.202100094

Cited by 8 publications

(6 citation statements)

References 209 publications

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“…As an example of hardness, the metastatic properties of cancer cells normally make them softer than normal cells, facilitating cell deformation (Plodinec et al, 2012). Also, the tissue around the cancer cells is harder than normal tissue, which is why breast cancer is diagnosed clinically by "palpating" the hard lump (Tian et al, 2022). This phenomenon is seen in many types of cancer.…”

Section: Cancermentioning

confidence: 99%

Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics

Liu,

Han,

Kong

et al. 2023

Microscopy Res & Technique

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Despite significant progress in human medicine, certain diseases remain challenging to promptly diagnose and treat. Hence, the imperative lies in the development of more exhaustive criteria and tools. Tissue and cellular mechanics exhibit distinctive traits in both normal and pathological states, suggesting that “force” represents a promising and distinctive target for disease diagnosis and treatment. Atomic force microscopy (AFM) holds great promise as a prospective clinical medical device due to its capability to concurrently assess surface morphology and mechanical characteristics of biological specimens within a physiological setting. This review presents a comprehensive examination of the operational principles of AFM and diverse mechanical models, focusing on its applications in investigating tissue and cellular mechanics associated with prevalent diseases. The findings from these studies lay a solid groundwork for potential clinical implementations of AFM.Research HighlightsBy examining the surface morphology and assessing tissue and cellular mechanics of biological specimens in a physiological setting, AFM shows promise as a clinical device to diagnose and treat challenging diseases.

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Section: Cancermentioning

confidence: 99%

Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics

Liu,

Han,

Kong

et al. 2023

Microscopy Res & Technique

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“…This intricate process, known as the invasion-metastasis cascade, comprises five fundamental stages: invasion, intravasation, circulation, extravasation, and colonization ( Fares et al, 2020 ; Babaei et al, 2021 ). The epithelial-mesenchymal transition (EMT) is widely recognized as the vital process of metastasis, which promotes the acquisition of malignant traits by cancer cells, while EMT is closely affected by extracellular matrix (EMC) hardness ( Tian et al, 2022 ). Cell scratch-wound healing and transwell invasion assays provided the initial evidence that paeonol markedly suppressed cancer cell migration and invasion, which was associated with the inhibition of MMP2 and MMP9 of the matrix metalloproteinase (MMP) family because MMP can decompose EMC ( Lyu et al, 2017 ).…”

Section: Paeonol Anticancer Effectsmentioning

confidence: 99%

Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy

Chang

Feng

et al. 2023

Front. Pharmacol.

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Cancer represents one of the leading causes of mortality worldwide. Conventional clinical treatments include radiation therapy, chemotherapy, immunotherapy, and targeted therapy. However, these treatments have inherent limitations, such as multidrug resistance and the induction of short- and long-term multiple organ damage, ultimately leading to a significant decrease in cancer survivors’ quality of life and life expectancy. Paeonol, a nature active compound derived from the root bark of the medicinal plant Paeonia suffruticosa, exhibits various pharmacological activities. Extensive research has demonstrated that paeonol exhibits substantial anticancer effects in various cancer, both in vitro and in vivo. Its underlying mechanisms involve the induction of apoptosis, the inhibition of cell proliferation, invasion and migration, angiogenesis, cell cycle arrest, autophagy, regulating tumor immunity and enhanced radiosensitivity, as well as the modulation of multiple signaling pathways, such as the PI3K/AKT and NF-κB signaling pathways. Additionally, paeonol can prevent adverse effects on the heart, liver, and kidneys induced by anticancer therapy. Despite numerous studies exploring paeonol’s therapeutic potential in cancer, no specific reviews have been conducted. Therefore, this review provides a systematic summary and analysis of paeonol’s anticancer effects, prevention of side effects, and the underlying mechanisms involved. This review aims to establish a theoretical basis for the adjunctive strategy of paeonol in cancer treatment, ultimately improving the survival rate and enhancing the quality of life for cancer patients.

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“…The extracellular matrix (ECM) contains the biomaterials required to support the organoid structure and mimic the cells’ biochemical and biophysical microenvironment. In addition to its biological functions, the matrix’s physical characteristics, such as stiffness and pliability can alter the biology, morphology, differentiation, and proliferative capacities of the cells [ 10 ]. Over the past decades, great advances in organoid engineering have been made thanks to the availability of a myriad of natural and synthetic scaffold materials.…”

Section: Introductionmentioning

confidence: 99%

Plasma-derived extracellular matrix for xenofree and cost-effective organoid modeling for hepatocellular carcinoma

El-Derby,

Khedr,

Ghoneim

et al. 2024

J Transl Med

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Background Hepatocellular carcinoma (HCC) causes significant cancer mortality worldwide. Cancer organoids can serve as useful disease models by high costs, complexity, and contamination risks from animal-derived products and extracellular matrix (ECM) that limit its applications. On the other hand, synthetic ECM alternatives also have limitations in mimicking native biocomplexity. This study explores the development of a physiologically relevant HCC organoid model using plasma-derived extracellular matrix as a scaffold and nutritive biomatrix with different cellularity components to better mimic the heterogenous HCC microenvironment. Plasma-rich platelet is recognized for its elevated levels of growth factors, which can promote cell proliferation. By employing it as a biomatrix for organoid culture there is a potential to enhance the quality and functionality of organoid models for diverse applications in biomedical research and regenerative medicine and to better replicate the heterogeneous microenvironment of HCC. Method To generate the liver cancer organoids, HUH-7 hepatoma cells were cultured alone (homogenous model) or with human bone marrow-derived mesenchymal stromal cells and human umbilical vein endothelial cells (heterogeneous model) in plasma-rich platelet extracellular matrix (ECM). The organoids were grown for 14 days and analyzed for cancer properties including cell viability, invasion, stemness, and drug resistance. Results HCC organoids were developed comprising HUH-7 hepatoma cells with or without human mesenchymal stromal and endothelial cells in plasma ECM scaffolds. Both homogeneous (HUH-7 only) and heterogeneous (mixed cellularity) organoids displayed viability, cancer hallmarks, and chemoresistance. The heterogeneous organoids showed enhanced invasion potential, cancer stem cell populations, and late-stage HCC genetic signatures versus homogeneous counterparts. Conclusion The engineered HCC organoids system offers a clinically relevant and cost-effective model to study liver cancer pathogenesis, stromal interactions, and drug resistance. The plasma ECM-based culture technique could enable standardized and reproducible HCC modeling. It could also provide a promising option for organoid culture and scaling up.

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Biophysics Role and Biomimetic Culture Systems of ECM Stiffness in Cancer EMT

Abstract: Figure 6. Perspectives for future ECM stiffness studies. Much work needs to be done, including identifying specific mechanisms in diverse cancers, deeply exploring the mechanism of ECM stiffness in tumor progression, and developing culture systems more akin to living tissues.

Cited by 8 publications

References 209 publications

Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics

Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics

Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy

Plasma-derived extracellular matrix for xenofree and cost-effective organoid modeling for hepatocellular carcinoma

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