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Deciphering Cell-to-Cell Communication in Acquisition of Cancer Traits: Extracellular Membrane Vesicles Are Regulators of Tissue Biomechanics

Pokharel, D., Wijesinghe, P., Oenarto, V., Lu, J.F., Sampson, David, Kennedy, B.F., Wallace, V.P. and Bebawy, M. (2016) Deciphering Cell-to-Cell Communication in Acquisition of Cancer Traits: Extracellular Membrane Vesicles Are Regulators of Tissue Biomechanics OMICS A Journal of Integrative Biology, 20 (8). pp. 462-469.

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Deciphering the role of cell-to-cell communication in acquisition of cancer traits such as metastasis is one of the key challenges of integrative biology and clinical oncology. In this context, extracellular vesicles (EVs) are important vectors in cell-to-cell communication and serve as conduits in the transfer of cellular constituents required for cell function and for the establishment of cellular phenotypes. In the case of malignancy, they have been shown to support the acquisition of common traits defined as constituting the hallmarks of cancer. Cellular biophysics has contributed to our understanding of some of these central traits with changes in tissue biomechanics reflective of cell state. Indeed, much is known about stiffness of the tissue scaffold in the context of cell invasion and migration. This article advances this knowledge frontier by showing for the first time that EVs are mediators of tissue biomechanical properties and, importantly, demonstrates a link between the acquisition of cancer multidrug resistance and increased tissue stiffness of the malignant mass. The methodology used in the study employed optical coherence elastography and atomic force microscopy on breast cancer cell monolayers and tumor spheroids. Specifically, we show here that the acquired changes in tissue stiffness can be attributed to the intracellular transfer of a protein complex comprising ezrin, radixin, moesin, CD44, and P-glycoprotein. This has important implications in facilitating mechano-transduced signaling cascades that regulate the acquisition of cancer traits, such as invasion and metastasis. Finally, this study also introduces novel targets and strategies for diagnostic and therapeutic innovation in oncology, with a view to prevention of metastatic spread and personalized medicine in cancer treatment.

Item Type: Article
Divisions : Faculty of Engineering and Physical Sciences
Faculty of Health and Medical Sciences
Authors :
Pokharel, D.
Wijesinghe, P.
Oenarto, V.
Lu, J.F.
Kennedy, B.F.
Wallace, V.P.
Bebawy, M.
Date : 2016
DOI : 10.1089/omi.2016.0072
Uncontrolled Keywords : ezrin, Hermes antigen, moesin, multidrug resistance protein, radixin, ABC transporter subfamily B, actin binding protein, CD44 protein, human, cytoskeleton protein, ezrin, hyaluronic acid binding protein, membrane protein, moesin, radixin, animal experiment, animal model, Article, atomic force microscopy, biomechanics, breast cancer, breast cancer cell line, cell communication, cell function, cell invasion, cell migration, controlled study, elastography, exosome, human, human cell, in vitro study, in vivo study, membrane vesicle, mouse, nonhuman, priority journal, tissue biomechanics, tissue scaffold, tumor spheroid, biomechanics, cell communication, exosome, genetics, neoplasm, personalized medicine, phenotype, signal transduction, tumor cell line, ATP Binding Cassette Transporter, Sub-Family B, Biomechanical Phenomena, Cell Communication, Cell Line, Tumor, Cytoskeletal Proteins, Extracellular Vesicles, Humans, Hyaluronan Receptors, Membrane Proteins, Microfilament Proteins, Neoplasms, Phenotype, Precision Medicine, Signal Transduction
Depositing User : Maria Rodriguez-Marquez
Date Deposited : 04 Jun 2018 09:37
Last Modified : 19 Sep 2018 11:32

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