Interpenetrating Polymer Network Hydrogels of Gelatin and Poly(ethylene glycol) as an Engineered 3D Tumor Microenvironment

Lee, Dong Shin; Kang, Jeon Il; Hwang, Byeong Hee; Park, Kyung Min

doi:10.1007/s13233-019-7072-x

Cited by 13 publications

(11 citation statements)

References 37 publications

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“…Matrix stiffness influences cell fate and behavior, and, therefore, researchers are progressively adjusting this parameter when performing experiments. Cancer models that included stiffness as a parameter have demonstrated that it can regulate epithelial-to-mesenchymal transition (EMT) [ 27 , 60 , 61 , 62 , 63 ], resistance to chemotherapy [ 19 , 31 , 55 ], cell proliferation [ 18 , 30 , 31 , 55 , 62 ], migration [ 24 , 64 , 65 ] and invasion [ 19 , 20 , 21 , 22 ]. However, the use of different matrices or the experimental temporality can yield contradicting results.…”

Section: Discussionmentioning

confidence: 99%

“…However, the use of different matrices or the experimental temporality can yield contradicting results. For example, increased stiffness has shown to promote proliferation in natural scaffolds, such as collagen type I [ 18 , 54 ] and alginate/Matrigel [ 62 ], while restricting proliferation in cells cultured in polymeric scaffolds [ 30 , 31 ]. Studies using synthetic matrices in a physiological stiffness range (0.1–20 kPa) reported that invasion is mostly promoted with increased stiffness, but it is inhibited at nonphysiological higher stiffness (>20 kPa) [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…The main advantage of using coated-PA gels is that they allow the increase in substrate stiffness without increasing the number of biological signals (e.g., adhesion sites), contrary to natural matrices, such as collagen I and rBM. On the other hand, three-dimensional models include cell embedding within polymeric matrices, usually functionalized with RGD or MMP-cleavable motifs [ 28 , 29 , 30 , 31 ], or within ECM-like matrices, such as collagen type I and basal membrane extracts [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

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Increased Stiffness Downregulates Focal Adhesion Kinase Expression in Pancreatic Cancer Cells Cultured in 3D Self-Assembling Peptide Scaffolds

et al. 2022

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The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that participates in integrin-mediated signal transduction and contributes to different biological processes, such as cell migration, survival, proliferation and angiogenesis. Moreover, FAK can be activated by autophosphorylation at position Y397 and trigger different signaling pathways in response to increased extracellular matrix stiffness. In addition, FAK is overexpressed and/or hyperactivated in many epithelial cancers, and its expression correlates with tumor malignancy and invasion potential. One of the characteristics of solid tumors is an over deposition of ECM components, which generates a stiff microenvironment that promotes, among other features, sustained cell proliferation and survival. Researchers are, therefore, increasingly developing cell culture models to mimic the increased stiffness associated with these kinds of tumors. In the present work, we have developed a new 3D in vitro model to study the effect of matrix stiffness in pancreatic ductal adenocarcinoma (PDAC) cells as this kind of tumor is characterized by a desmoplastic stroma and an increased stiffness compared to its normal counterpart. For that, we have used a synthetic self-assembling peptide nanofiber matrix, RAD16-I, which does not suffer a significant degradation in vitro, thus allowing to maintain the same local stiffness along culture time. We show that increased matrix stiffness in synthetic 3D RAD16-I gels, but not in collagen type I scaffolds, promotes FAK downregulation at a protein level in all the cell lines analyzed. Moreover, even though it has classically been described that stiff 3D matrices promote an increase in pFAKY397/FAK proteins, we found that this ratio in soft and stiff RAD16-I gels is cell-type-dependent. This study highlights how cell response to increased matrix stiffness greatly depends on the nature of the matrix used for 3D culture.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased Stiffness Downregulates Focal Adhesion Kinase Expression in Pancreatic Cancer Cells Cultured in 3D Self-Assembling Peptide Scaffolds

et al. 2022

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“…Some popular 3D cancer models include scaffold-free spheroids [ 212 , 213 ], hydrogels and other biomaterials-based models [ 213 , 214 , 215 , 216 , 217 , 218 , 219 ], and microfluidic devices [ 219 ]. Scaffold-free spheroids provide a unique opportunity to isolate and study cellular interactions, including the importance of cancer-associated fibroblasts (CAF) in protease activity and cancer metastasis.…”

Section: Protease Targeting Nanomedicine In Ovcamentioning

confidence: 99%

The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine

O’Connell

VandenHeuvel

Kamat

et al. 2022

IJMS

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Ovarian cancer (OvCa) is one of the leading causes of mortality globally with an overall 5-year survival of 47%. The predominant subtype of OvCa is epithelial carcinoma, which can be highly aggressive. This review launches with a summary of the clinical features of OvCa, including staging and current techniques for diagnosis and therapy. Further, the important role of proteases in OvCa progression and dissemination is described. Proteases contribute to tumor angiogenesis, remodeling of extracellular matrix, migration and invasion, major processes in OvCa pathology. Multiple proteases, such as metalloproteinases, trypsin, cathepsin and others, are overexpressed in the tumor tissue. Presence of these catabolic enzymes in OvCa tissue can be exploited for improving early diagnosis and therapeutic options in advanced cases. Nanomedicine, being on the interface of molecular and cellular scales, can be designed to be activated by proteases in the OvCa microenvironment. Various types of protease-enabled nanomedicines are described and the studies that focus on their diagnostic, therapeutic and theranostic potential are reviewed.

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“…Hydrogels are colloids composed of a hydrophilic polymer with a high water content and a three-dimensional (3D) crosslinked networks structure, 1 widely used in tissue engineering, biomedicine and other elds. [2][3][4] Traditional hydrogels have defects such as poor mechanical properties 5 and single performance, 6 and their application in biomedicine is signicantly limited. In recent years, with the development of life sciences, people have submitted higher requirements for hydrogels.…”

Section: Introductionmentioning

confidence: 99%