Extracellular matrix mechanobiology in cancer cell migration

Vasudevan, Jyothsna; Jiang, Kuan; Fernandez, Javier G.; Lim, Chwee Teck

doi:10.1016/j.actbio.2022.10.016

Cited by 24 publications

(17 citation statements)

References 189 publications

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“…27 In the past, mechanobiology research has mainly focused on abnormal tumor ECM and the invasion behaviors of cancer cells. 28 As an initial factor in OTM, mechanical force also plays a vital role in ECM deformation and biological cell reactions in the periodontium. PDLCs are essential mechanosensory cells that participate in periodontal remodeling.…”

Section: Discussionmentioning

confidence: 99%

LncRNAADAMTS9‐AS2 regulates periodontal ligament cell migration under mechanical compression via ADAMTS9/fibronectin

Yu,

Guo,

Yang

et al. 2023

J of Periodontal Research

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BackgroundPeriodontal ligament cells (PDLCs) are key mechanosensory cells involved in extracellular matrix (ECM) remodeling during orthodontic tooth movement (OTM). Mechanical force changes the ECM components, such as collagens and matrix metalloproteinases. However, the associations between the changes in ECM molecules and cellular dynamics during OTM remain largely uncharacterized.ObjectivesTo investigate the influence of mechanical force on the morphology and migration of PDLCs and explore the interaction between ECM remodeling and cellular dynamics, including the detailed mechanisms involved.MethodsHuman PDLCs (hPDLCs) were subjected to a static mechanical compression to mimic the compression state of OTM in vitro. A mouse OTM model was used to mimic the OTM procedure in vivo. The migration of hPDLCs was compared by wound healing and transwell migration assays. Moreover, expression levels of ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) and fibronectin (FN) in hPDLCs were determined via western blotting, immunofluorescence staining, and enzyme‐linked immunosorbent assays. Expression levels of ADAMTS9 and FN in mice were assessed via immunohistochemical staining. Additionally, the relative expression of long non‐coding RNA (lncRNA) ADAMTS9‐antisense RNA 2 (ADAMTS9‐AS2) was assessed via quantitative real‐time polymerase chain reaction. ADAMTS9‐AS2 knockdown was performed to confirm its function in hPDLCs.ResultsMechanical compression induced changes in the morphology of hPDLCs. It also promoted migration and simultaneous upregulation of FN and downregulation of ADAMTS9, a fibronectinase. The mouse OTM model showed the same expression patterns of the two proteins on the compression side of the periodontium of the moved teeth. RNA sequencing revealed that lncRNA ADAMTS9‐AS2 expression was significantly upregulated in hPDLCs under mechanical compression. After knocking down ADAMTS9‐AS2, hPDLCs migration was significantly inhibited. ADAMTS9 expression was increased as FN expression decreased compared to that in the control group. Moreover, knockdown of ADAMTS9‐AS2 reduced the effect of mechanical compression on hPDLCs migration and reversed the expression change of ADAMTS9 and FN. RNA immunoprecipitation revealed direct binding between ADAMTS9‐AS2 and ADAMTS9 protein.ConclusionOur study suggests that mechanical compression induces the expression of ADAMTS9‐AS2, which directly binds to ADAMTS9 and inhibits its function, leading to the promotion of downstream FN expression and ECM remodeling to facilitate hPDLCs migration and maintain the stability of the periodontium.

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Section: Discussionmentioning

confidence: 99%

LncRNAADAMTS9‐AS2 regulates periodontal ligament cell migration under mechanical compression via ADAMTS9/fibronectin

Yu,

Guo,

Yang

et al. 2023

J of Periodontal Research

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“…In addition, the dynamic nature of TME-ECM, the characteristics of disease-specific mechanics and biomolecular complexity will establish an abnormal feedback loop. 184 If not handled properly, it will lead to further imbalance of cancer cells and related tissues. 185 In the preparation of decellularized matrices-based hybrid biomaterials, cross-linking reaction is essential, but overreaction has been proved to have adverse effects on the composition and biological activity of the matrix.…”

Section: Standardization Of Decellularization Protocolmentioning

confidence: 99%

“…What is more important, a librarian based upon clinical cancer samples is indispensable alternative to carry out the researches. In addition, the dynamic nature of TME–ECM, the characteristics of disease‐specific mechanics and biomolecular complexity will establish an abnormal feedback loop 184 . If not handled properly, it will lead to further imbalance of cancer cells and related tissues 185 .…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

Decellularized diseased tissues: current state‐of‐the‐art and future directions

Li,

Shan,

Chen

et al. 2023

MedComm

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Decellularized matrices derived from diseased tissues/organs have evolved in the most recent years, providing novel research perspectives for understanding disease occurrence and progression and providing accurate pseudo models for developing new disease treatments. Although decellularized matrix maintaining the native composition, ultrastructure, and biomechanical characteristics of extracellular matrix (ECM), alongside intact and perfusable vascular compartments, facilitates the construction of bioengineered organ explants in vitro and promotes angiogenesis and tissue/organ regeneration in vivo, the availability of healthy tissues and organs for the preparation of decellularized ECM materials is limited. In this paper, we review the research advancements in decellularized diseased matrices. Considering that current research focuses on the matrices derived from cancers and fibrotic organs (mainly fibrotic kidney, lungs, and liver), the pathological characterizations and the applications of these diseased matrices are mainly discussed. Additionally, a contrastive analysis between the decellularized diseased matrices and decellularized healthy matrices, along with the development in vitro 3D models, is discussed in this paper. And last, we have provided the challenges and future directions in this review. Deep and comprehensive research on decellularized diseased tissues and organs will promote in‐depth exploration of source materials in tissue engineering field, thus providing new ideas for clinical transformation.

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“…In this context, the storage or elastic modulus appears to be a pivotal feature, which can be modulated to mimic the G ′ of the natural ECM or to impact the cell fate. 32–34 Despite the several advantages of gels for biomedical applications, only a few studies have focused on controlling the stiffness of bioinspired LMWGs via light irradiation. 35,36…”

mentioning

confidence: 99%

“…In this context, the storage or elastic modulus appears to be a pivotal feature, which can be modulated to mimic the G 0 of the natural ECM or to impact the cell fate. [32][33][34] Despite the several advantages of gels for biomedical applications, only a few studies have focused on controlling the stiffness of bioinspired LMWGs via light irradiation. 35,36 In this contribution, we designed a photo-cleavable low molecular weight gelator based on bioinspired and biocompatible architecture glyconucleo-bolaamphiphile (GNBA).…”

mentioning

confidence: 99%