ECM stiffness-tuned exosomes drive breast cancer motility through thrombospondin-1

Patwardhan, Sejal; Mahadik, Pratiksha; Shetty, Omshree; Sen, Shamik

doi:10.1016/j.biomaterials.2021.121185

Cited by 63 publications

(29 citation statements)

References 69 publications

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“…Furthermore, the inhibition of certain integrins may have an effect on YAP activation and subsequent CAF-activation based exosome secretion. Although this CAF-specific mechanism has not been fully elucidated, ECM stiffness was found to induce exosome secretion in breast cancer cells through a YAP pathway dependent mechanism in breast cancer [46] . Evidence to confirm that a similar mechanism may be at play in the pancreas has not been uncovered, but recent work showing how extracellular vesicles from pancreatic cancer stem cells modulate YAP activity in PDAC cells hints that exosomes may modulate cells in the TME through the same mechanism [47] .…”

Section: Discussionmentioning

confidence: 99%

Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model

Xiao

Pahlavanneshan

Eun

et al. 2022

Matrix Biology Plus

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Section: Discussionmentioning

confidence: 99%

Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model

Xiao

Pahlavanneshan

Eun

et al. 2022

Matrix Biology Plus

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“…Interestingly, exosome-enriched fractions were able to potentiate invadopodia formation and stability ( Hoshino et al, 2013 ). Intriguingly, ECM stiffness has been shown to increase invadopodia formation ( Alexander et al, 2008 ) and to enhance exosome secretion and modify exosome contents (e.g., MMPs) ( Patwardhan et al, 2021 ), supporting the notion of an intricate relationship between invadopodia and exosomes.…”

Section: Mmps In Extracellular Vesicles and Relation With Invadopodiamentioning

confidence: 92%

“…These alterations are triggered by diverse signals, coming from the tumor itself or from the tumor microenvironment, such as hypoxia or chemotherapeutic drugs ( Bebelman et al, 2021 ). In breast cancer, the stiffness of ECM that is correlated to tumor progression has been directly implicated in the increase of EV secretion and cancer cell migration ( Patwardhan et al, 2021 ). Finally, several in vivo studies indicate that depletion of EVs reduces tumor progression and metastasis ( Peinado et al, 2012 ; Kosaka et al, 2013 ; Tickner et al, 2014 ; Costa-Silva et al, 2015 ; Nishida-Aoki et al, 2017 ).…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

A Journey on Extracellular Vesicles for Matrix Metalloproteinases: A Mechanistic Perspective

Thuault

Ghossoub

Gourichon

et al. 2022

Front. Cell Dev. Biol.

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Matrix metalloproteinases (MMPs) are key players in matrix remodeling and their function has been particularly investigated in cancer biology. Indeed, through extracellular matrix (ECM) degradation and shedding of diverse cell surface macromolecules, they are implicated in different steps of tumor development, from local expansion by growth to tissue invasion and metastasis. Interestingly, MMPs are also components of extracellular vesicles (EVs). EVs are membrane-limited organelles that cells release in their extracellular environment. These “secreted” vesicles are now well accepted players in cell-to-cell communication. EVs have received a lot of interest in recent years as they are also envisioned as sources of biomarkers and as potentially outperforming vehicles for the delivery of therapeutics. Molecular machineries governing EV biogenesis, cargo loading and delivery to recipient cells are complex and still under intense investigation. In this review, we will summarize the state of the art of our knowledge about the molecular mechanisms implicated in MMP trafficking and secretion. We focus on MT1-MMP, a major effector of invasive cell behavior. We will also discuss how this knowledge is of interest for a better understanding of EV-loading of MMPs. Such knowledge might be of use to engineer novel strategies for cancer treatment. A better understanding of these mechanisms could also be used to design more efficient EV-based therapies.

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“…To demonstrate the role of exosomes in ECM stiffness-triggered breast cancer invasiveness, Patwardhan et al fabricated stiffness-tunable polyacrylamide (PA) gels as ECM mimics ( Figure 3 ). Interestingly, stiff ECM cultures fostered exosome secretion by a series of changes in cell morphology, adhesion, and protrusion dynamics, which resulted in the invasion of breast cancer cells [ 146 ]. Aberrant cell behaviors can be induced by in vitro 2D culture, and the heterogeneity of exosomal behaviors also depends on the culture conditions [ 147 ].…”

Section: Biomedical Exploitation Of Exosomes Delivered In Hydrogelsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Hydrogels for Exosome Delivery in Biomedical Applications

Xie

Guan

Guo

et al. 2022

Gels

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Hydrogels, which are hydrophilic polymer networks, have attracted great attention, and significant advances in their biological and biomedical applications, such as for drug delivery, tissue engineering, and models for medical studies, have been made. Due to their similarity in physiological structure, hydrogels are highly compatible with extracellular matrices and biological tissues and can be used as both carriers and matrices to encapsulate cellular secretions. As small extracellular vesicles secreted by nearly all mammalian cells to mediate cell–cell interactions, exosomes play very important roles in therapeutic approaches and disease diagnosis. To maintain their biological activity and achieve controlled release, a strategy that embeds exosomes in hydrogels as a composite system has been focused on in recent studies. Therefore, this review aims to provide a thorough overview of the use of composite hydrogels for embedding exosomes in medical applications, including the resources for making hydrogels and the properties of hydrogels, and strategies for their combination with exosomes.

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ECM stiffness-tuned exosomes drive breast cancer motility through thrombospondin-1

Cited by 63 publications

References 69 publications

Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model

Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model

A Journey on Extracellular Vesicles for Matrix Metalloproteinases: A Mechanistic Perspective

Hydrogels for Exosome Delivery in Biomedical Applications

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