Decellularized Extracellular Matrix for Cancer Research

Genetic mutation and alterations of intracellular signaling have been focused on to understand the mechanisms of oncogenesis and cancer progression. Currently, it is pointed out to consider cancer as tissues. The extracellular microenvironment, including the extracellular matrix (ECM), is important for the regulation of cancer cell behavior. To comprehensively investigate ECM roles in the regulation of cancer cell behavior, decellularized ECM (dECM) is now used as an in vitro ECM model. In this review, I classify dECM with respect to its sources and summarize the preparation and characterization methods for dECM. Additionally, the examples of cancer research using the dECM were introduced. Finally, future perspectives of cancer studies with dECM are described in the conclusions.

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Differing Roles of Hyaluronan Molecular Weight on Cancer Cell Behavior and Chemotherapy Resistance

Cancers ◽

10.3390/cancers10120482 ◽

2018 ◽

Vol 10 (12) ◽

pp. 482 ◽

Cited By ~ 17

Author(s):

Zoe Price ◽

Noor Lokman ◽

Carmela Ricciardelli

Keyword(s):

Molecular Weight ◽

Tyrosine Kinase ◽

Cancer Cell ◽

Cancer Progression ◽

Receptor Tyrosine Kinase ◽

Intracellular Signaling ◽

Therapy Resistance ◽

Cell Behavior ◽

Mesenchymal Transition

Hyaluronan (HA), a glycosaminoglycan located in the extracellular matrix, is important in embryo development, inflammation, wound healing and cancer. There is an extensive body of research demonstrating the role of HA in all stages of cancer, from initiation to relapse and therapy resistance. HA interacts with multiple cell surface receptors, including CD44, receptor for hyaluronan mediated motility (RHAMM) and intracellular signaling pathways, including receptor tyrosine kinase pathways, to promote the survival and proliferation of cancer cells. Additionally, HA promotes the formation of cancer stem cell (CSC) populations, which are hypothesized to be responsible for the initiation of tumors and therapy resistance. Recent studies have identified that the molecular weight of HA plays differing roles on both normal and cancer cell behavior. This review explores the role of HA in cancer progression and therapy resistance and how its molecular weight is important in regulating CSC populations, epithelial to mesenchymal transition (EMT), ATP binding cassette (ABC) transporter expression and receptor tyrosine kinase pathways.

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Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

Cancer Gene Therapy ◽

10.1038/s41417-021-00293-w ◽

2021 ◽

Author(s):

Jiongwei Pan ◽

Gang Huang ◽

Zhangyong Yin ◽

Xiaoping Cai ◽

Enhui Gong ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cancer Progression ◽

Lung Cancer Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

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P2X7 Receptor Promotes Mouse Mammary Cancer Cell Invasiveness and Tumour Progression, and Is a Target for Anticancer Treatment

Cancers ◽

10.3390/cancers12092342 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2342 ◽

Cited By ~ 3

Author(s):

Lucie Brisson ◽

Stéphanie Chadet ◽

Osbaldo Lopez-Charcas ◽

Bilel Jelassi ◽

David Ternant ◽

...

Keyword(s):

Cancer Cells ◽

Cancer Cell ◽

Cancer Progression ◽

P2x7 Receptor ◽

Mammary Cancer ◽

Tumour Progression ◽

Mammary Cancer Cell ◽

Cell Invasiveness ◽

Cancer Cell Invasiveness

The P2X7 receptor is an ATP-gated cation channel with a still ambiguous role in cancer progression, proposed to be either pro- or anti-cancerous, depending on the cancer or cell type in the tumour. Its role in mammary cancer progression is not yet defined. Here, we show that P2X7 receptor is functional in highly aggressive mammary cancer cells, and induces a change in cell morphology with fast F-actin reorganization and formation of filopodia, and promotes cancer cell invasiveness through both 2- and 3-dimensional extracellular matrices in vitro. Furthermore, P2X7 receptor sustains Cdc42 activity and the acquisition of a mesenchymal phenotype. In an immunocompetent mouse mammary cancer model, we reveal that the expression of P2X7 receptor in cancer cells, but not in the host mice, promotes tumour growth and metastasis development, which were reduced by treatment with specific P2X7 antagonists. Our results demonstrate that P2X7 receptor drives mammary tumour progression and represents a pertinent target for mammary cancer treatment.

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Investigation of an injectable gold nanoparticle extracellular matrix

Journal of Biomaterials Applications ◽

10.1177/08853282211051586 ◽

2021 ◽

pp. 088532822110515

Author(s):

Colten Snider ◽

David Grant ◽

Sheila A Grant

Keyword(s):

Extracellular Matrix ◽

Synovial Fibroblasts ◽

X Ray ◽

Decellularized Extracellular Matrix ◽

Intracellular Ros ◽

Murine Fibroblasts ◽

Post Traumatic ◽

Injection Force ◽

20 Nm

Post-traumatic osteoarthritis (PTOA) is a progressive articular degenerative disease that degrades articular cartilage and stimulates apoptosis in chondrocyte cells. An injectable decellularized, extracellular matrix (ECM) scaffold, that might be able to combat the effects of PTOA, was developed where the ECM was conjugated with 20 nm gold nanoparticles (AuNP) and supplemented with curcumin and hyaluronic acid (HA). Porcine diaphragm ECM was decellularized and homogenized; AuNPs were conjugated using chemical crosslinking followed by mixing with curcumin and/or HA. Injection force testing and scanning electron microscopy with energy-dispersive X-ray spectroscopy were utilized to characterize the ECM scaffolds. In vitro testing with L929 murine fibroblasts, equine synovial fibroblasts, and Human Chondrocytes were used to determine biocompatibility, reactive oxygen species (ROS) reduction, and chondroprotective ability. The results demonstrated that conjugation of 20 nm AuNPs to the ECM was successful without significantly altering the physical properties as noted in the low injection force. In vitro work provided evidence of biocompatibility with a propensity to reduce intracellular ROS and an ability to mitigate apoptosis of chondrocyte cells stimulated with IL-1β, a known apoptosis inducing cytokine. It was concluded that an injectable AuNP-ECM may have the ability to mitigate inflammation and apoptosis.

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Dietary Antioxidant Trans-Cinnamaldehyde Reduced Visfatin-Induced Breast Cancer Progression: In Vivo and In Vitro Study

Antioxidants ◽

10.3390/antiox8120625 ◽

2019 ◽

Vol 8 (12) ◽

pp. 625 ◽

Cited By ~ 3

Author(s):

Yi-Fen Chiang ◽

Hsin-Yuan Chen ◽

Ko-Chieh Huang ◽

Po-Han Lin ◽

Shih-Min Hsia

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Progression ◽

Natural Compound ◽

Cancer Cell Line ◽

Nad Synthesis

Excessive growth of cancer cells is the main cause of cancer mortality. Therefore, discovering how to inhibit cancer growth is an important research topic. Recently, the newly discovered adipokine, known as nicotinamide phosphoribosyl transferase (NAMPT, visfatin), which has been associated with metabolic syndrome and obesity, has also been found to be a major cause of cancer proliferation. Therefore, inhibition of NAMPT and reduction of Nicotinamide adenine dinucleotide (NAD) synthesis is one strategy for cancer therapy. Cinnamaldehyde (CA), as an antioxidant and anticancer natural compound, may have the ability to inhibit visfatin. The breast cancer cell line and xenograft animal models were treated under different dosages of visfatin combined with CA and FK866 (a visfatin inhibitor) to test for cell toxicity, as well as inhibition of tumor-related proliferation of protein expression. In the breast cancer cell and the xenograft animal model, visfatin significantly increased proliferation-related protein expression, but combination with CA or FK866 significantly reduced visfatin-induced carcinogenic effects. For the first time, a natural compound inhibiting extracellular and intracellular NAMPT has been demonstrated. We hope that, in the future, this can be used as a potential anticancer compound and provide further directions for research.

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Dynamics of 3D carcinoma cell invasion into aligned collagen

Integrative Biology ◽

10.1039/c7ib00152e ◽

2018 ◽

Vol 10 (2) ◽

pp. 100-112 ◽

Cited By ~ 12

Author(s):

Arja Ray ◽

Rachel K. Morford ◽

Nima Ghaderi ◽

David J. Odde ◽

Paolo. P. Provenzano

Keyword(s):

Extracellular Matrix ◽

Cancer Cell ◽

Cell Invasion ◽

Carcinoma Cell ◽

Spatiotemporal Dynamics ◽

Contact Inhibition ◽

Contact Guidance ◽

Cell Behavior ◽

Cancer Cell Invasion ◽

Invasive Front

We present a novel platform to quantify spatiotemporal dynamics of cell behavior at and beyond the invasive front and demonstrate that contact inhibition and contact guidance orchestrate cancer cell invasion into anisotropic extracellular matrix.

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The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation

Cancers ◽

10.3390/cancers11121968 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1968 ◽

Cited By ~ 6

Author(s):

Danilo Predes ◽

Luiz F. S. Oliveira ◽

Laís S. S. Ferreira ◽

Lorena A. Maia ◽

João M. A. Delou ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cell ◽

Cancer Progression ◽

Active Form ◽

Colorectal Cancer Cell ◽

Intestinal Cell ◽

Transcriptional Level ◽

Mice Model

The deregulation of the Wnt/β-catenin signaling pathway is a central event in colorectal cancer progression, thus a promising target for drug development. Many natural compounds, such as flavonoids, have been described as Wnt/β-catenin inhibitors and consequently modulate important biological processes like inflammation, redox balance, cancer promotion and progress, as well as cancer cell death. In this context, we identified the chalcone lonchocarpin isolated from Lonchocarpus sericeus as a Wnt/β-catenin pathway inhibitor, both in vitro and in vivo. Lonchocarpin impairs β-catenin nuclear localization and also inhibits the constitutively active form of TCF4, dnTCF4-VP16. Xenopus laevis embryology assays suggest that lonchocarpin acts at the transcriptional level. Additionally, we described lonchocarpin inhibitory effects on cell migration and cell proliferation on HCT116, SW480, and DLD-1 colorectal cancer cell lines, without any detectable effects on the non-tumoral intestinal cell line IEC-6. Moreover, lonchocarpin reduces tumor proliferation on the colorectal cancer AOM/DSS mice model. Taken together, our results support lonchocarpin as a novel Wnt/β-catenin inhibitor compound that impairs colorectal cancer cell growth in vitro and in vivo.

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The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion

Endocrine Related Cancer ◽

10.1677/erc.1.01136 ◽

2006 ◽

Vol 13 (3) ◽

pp. 895-903 ◽

Cited By ~ 35

Author(s):

J R Puddefoot ◽

U K I Udeozo ◽

S Barker ◽

G P Vinson

Keyword(s):

Breast Cancer ◽

Cell Adhesion ◽

Angiotensin Ii ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Progression ◽

Renin Angiotensin System ◽

Adhesion And Invasion

As breast cancer remains the most common cause of cancer death in women, there is a continuing need not only to further characterise the processes of cancer progression, but also to improve accuracy of prognostic markers. Breast epithelial cells express components of the renin angiotensin system and studies suggest that these may be altered in disease progression. In addition, altered integrin expression correlates with lymph node metastasis. The aim of this study was to investigate the relationship between angiotensin II (AII) and integrins in breast tissue and, in particular, their role in breast cancer cell metastasis. Using in vitro assays, AII (10−6 M)-treated MCF-7 and T47D breast cancer cells both show reduced adhesion to extracellular matrix proteins collagen-, fibronectin- and laminin-coated wells (P<0.001) and reduced invasion through collagen-, fibronectin- and laminin-coated membranes (P<0.05). This action was inhibited by co-treatment with the angiotensin type 1 receptor (AT1R) antagonist losartan (10−5 M). The addition of the AT2R inhibitor PD123319 (10−5 M) to AII-treated cells had no significant effect. Semi-quantitative reverse transcriptase-PCR and western blotting revealed that cells treated with AII (10−6 M) expressed lower levels of both integrin α3 and β1. Using specific inhibitors, this was shown to occur through protein kinase C signalling. These data suggest that AII reduces cell adhesion and invasion through the type 1 receptor and that this effect may be due to reduced expression of integrins, and in particular α3 and β1.

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