Mechanobiology of solid tumors

Gargalionis, Antonios N.; Papavassiliou, Kostas A.; Papavassiliou, Athanasios G.

doi:10.1016/j.bbadis.2022.166555

Cited by 14 publications

(10 citation statements)

References 81 publications

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“…Tumor ECM has dynamic features and a pronounced effect on supporting TME vascularization [ 113 ]. It also (i) presents a physical barrier for drug perfusion; (ii) induces cell adhesion-mediated drug resistance owing to the elevated presence of ECM proteins; (iii) activates glycolysis and glutamine metabolism to provide an abundant energy supply for tumor cells; (iv) promotes aggressiveness and metastasis by the deposition of malignant cells to the tumor endothelium [ 112 , 113 , 114 ]. Various factors participate in ECM maintenance, including growth factors (VEGF, PDGF, Ang, stromal cell derived factor, SCDF) and proteins (MMP family).…”

Section: Nanomedicines For Targeting Tme: Application Of Natural and ...mentioning

confidence: 99%

Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments

Avgoustakis,

Angelopoulou

2024

Pharmaceutics

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Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays a crucial role in the clinical therapeutic outcome of conventional treatments and innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering the challenges of the tumor microenvironment (TME), in respect of effective drug accumulation and activity at the tumor site. The main focus is to overcome the obstacles of abnormal vasculature, dense stroma, extracellular matrix, hypoxia, and pH gradient acidosis. In this endeavor, nanomedicines that are targeting distinct features of TME have flourished; these aim to increase site specificity and achieve deep tumor penetration. Recently, research efforts have focused on the immune reprograming of TME in order to promote suppression of cancer stem cells and prevention of metastasis. Thereby, several nanomedicine therapeutics which have shown promise in preclinical studies have entered clinical trials or are already in clinical practice. Various novel strategies were employed in preclinical studies and clinical trials. Among them, nanomedicines based on biomaterials show great promise in improving the therapeutic efficacy, reducing side effects, and promoting synergistic activity for TME responsive targeting. In this review, we focused on the targeting mechanisms of nanomedicines in response to the microenvironment of solid tumors. We describe responsive nanomedicines which take advantage of biomaterials’ properties to exploit the features of TME or overcome the obstacles posed by TME. The development of such systems has significantly advanced the application of biomaterials in combinational therapies and in immunotherapies for improved anticancer effectiveness.

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Section: Nanomedicines For Targeting Tme: Application Of Natural and ...mentioning

confidence: 99%

Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments

Avgoustakis,

Angelopoulou

2024

Pharmaceutics

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“…Mechanotransduction is the process whereby mechanical stimuli emanating from the microenvironment are detected by mechanosensory proteins on the cell surface and, in turn, translated into biochemical signals within the cell that ultimately affect gene expression. Mechanobiology plays a fundamental role in cancer pathobiology, and numerous players that participate in tumor-related mechanotransduction have been identified [ 48 ]. Among them, YAP and TAZ have been characterized as key mechanosensors and mechanotransducers in tumor mechanobiology [ 49 , 50 ].…”

Section: Future Perspectives: Targeting the Interaction Between Yap/t...mentioning

confidence: 99%

Targeting YAP/TAZ in Combination with PD-L1 Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC)

Papavassiliou

Μαρίνος

Papavassiliou

2023

Cells

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The survival of non-small cell lung cancer (NSCLC) patients has improved in the last decade as a result of introducing new therapeutics, such as immune checkpoint inhibitors, in the clinic. Still, some NSCLC patients do not benefit from these therapies due to intrinsic resistance or the development of acquired resistance and their malignant disease progresses. Further research on the molecular underpinnings of NSCLC pathobiology is required in order to discover clinically relevant molecular targets that regulate tumor immunity and to develop reasonable therapeutic combinations that will promote the efficacy of immune checkpoint inhibitors. Yes-associated Protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), the final effectors of the Hippo signaling transduction pathway, are emerging as key players in NSCLC development and progression. Herein, we overview studies that have investigated the oncogenic role of YAP/TAZ in NSCLC, focusing on immune evasion, and highlight the therapeutic potential of combining YAP/TAZ inhibitory agents with immune checkpoint inhibitors for the management of NSCLC patients.

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“…The role of mechanical properties of cancer cells [4] as well as that of the microenvironment, including cell or matrix stiffness, has only been studied in recent years. Most of the studies investigated the mechanical properties of tumor cells growing in cell cultures in a two-dimensional substrate dish.…”

Section: Introductionmentioning

confidence: 99%

“…Tumors produce ECM components, proteolytically degrade ECM components, and bind and exert forces onto ECM components through adhesion receptors such as integrins [3, 13]. In turn, the chemical, mechanical, and structural features of the ECM fibrous network influence tumor growth and therapy response as well as tumour cell motility and invasion [4, 14–16]. For example, cancer cells often show increased collagen degradation and remodeling compared to normal cells, which in this way contribute to the formation of invasive tumors [17].…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Local Stress Analysis in Tumoroids

Rodrigues de Mercado,

Beslmüller,

Vorselen

et al. 2024

Preprint

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The reciprocal interplay between cancer cells and their local environment, mediated by mechanical forces, necessitates a deeper experimental understanding. This requires precise quantitative measurements of cellular forces within the intricate three-dimensional context of the extracellular matrix. While methods such as traction-force microscopy and micropillar-array technology have effectively reported on cellular forces in two-dimensional cell culture, extending these techniques to three dimensions has proven exceedingly challenging. In the current study, we introduced a novel approach utilizing soft, elastic hydrogel microparticles, resembling the size of cells, to serve as specific and sensitive traction probes in three-dimensional cell culture of collagen-embedded tumoroids. Our methodology relies on high-resolution detection of microparticle deformations. These deformations are translated into spatially resolved traction fields, reaching a spatial resolution down to 1 um and thereby detecting traction forces as low as 30 Pa. By integrating this high-resolution traction analysis with three-dimensional cell segmentation, we reconstructed the traction fields originating from individual cells. Our methodology enables us to explore the relationships between cellular characteristics, extracellular traction fields, and cellular responses. We observed that cellular stresses ranged from 10 to 100 Pa, integrating to cellular forces from 0.1 to 100 nN, which correlated with the localization of the cells actin skeleton, and the interaction area that cells developed towards the microparticles. Interestingly, the interaction of cells with inert microparticles appeared to be governed by contact mechanics resembling that two soft particles. The methodology presented here not only addresses the challenges of extending traditional stress-probe techniques to three dimensions, but also opens a strategy for the study of specific interactions between cells and the local tumoroid environment in a strive to fully understand cell-matrix reciprocity in tissue.

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Mechanobiology of solid tumors

Cited by 14 publications

References 81 publications

Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments

Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments

Targeting YAP/TAZ in Combination with PD-L1 Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (NSCLC)

Single-Cell Local Stress Analysis in Tumoroids

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