For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
9
views
4
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      489
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Tumor suppression by stromal TIMPs

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The tumor stroma has the capacity to drive cancer progression, although the mechanisms governing these effects are incompletely understood. Recently, we reported that deletion of tissue inhibitor of metalloproteinases (Timps) in fibroblasts unleashes the function of cancer-associated fibroblasts and identifies a novel mode of stromal–tumor communication that activates key oncogenic pathways invoving Notch and ras homolog gene family, member A (RhoA) via stromal exosomes.

          Related collections

          Most cited references4

          • Record: found
          • Abstract: found
          • Article: not found

          Carcinoma-associated fibroblasts are a rate-limiting determinant for tumour progression

          Masayuki Shimoda, Kieran Mellody, Akira Orimo (2010)
          Tumours are highly complex tissues composed of carcinoma cells and surrounding stroma, which is constructed by various different types of mesenchymal cells and an extracellular matrix (ECM). Carcinoma-associated fibroblasts (CAFs), which consist of both fibroblasts and myofibroblasts, are frequently observed in the stroma of human carcinomas, and their presence in large numbers is often associated with the development of high-grade malignancies and poor prognoses. Moreover, in human tumour xenograft models, CAFs extracted from the tumour are more capable of promoting tumour growth through their interactions with carcinoma cells when compared to those isolated from non-cancerous stroma. Taken together, these observations strongly suggest that CAFs actively contribute to tumour progression. In this review we highlight the emerging roles of these cells in promoting tumourigenesis, and we discuss the molecular mechanisms underlying their tumour-promoting capabilities and their cellular origin.
          Article 0 comments Cited 106 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44.

            François Le Loc'h, Paul Gutwein, S Runz … (2006)
            Ectodomain shedding is a proteolytic mechanism by which transmembrane molecules are converted into a soluble form. Cleavage is mediated by metalloproteases and proceeds in a constitutive or inducible fashion. Although believed to be a cell-surface event, there is increasing evidence that cleavage can take place in intracellular compartments. However, it is unknown how cleaved soluble molecules get access to the extracellular space. By analysing L1 (CD171) and CD44 in ovarian carcinoma cells, we show in the present paper that the cleavage induced by ionomycin, APMA (4-aminophenylmercuric acetate) or MCD (methyl-beta-cyclodextrin) is initiated in an endosomal compartment that is subsequently released in the form of exosomes. Calcium influx augmented the release of exosomes containing functionally active forms of ADAM10 (a disintegrin and metalloprotease 10) and ADAM17 [TACE (tumour necrosis factor a-converting enzyme)] as well as CD44 and L1 cytoplasmic cleavage fragments. Cleavage could also proceed in released exosomes, but only depletion of ADAM10 by small interfering RNA blocked cleavage under constitutive and induced conditions. In contrast, cleavage of L1 in response to PMA occurred at the cell surface and was mediated by ADAM17. We conclude that different ADAMs are involved in distinct cellular compartments and that ADAM10 is responsible for shedding in vesicles. Our findings open up the possibility that exosomes serve as a platform for ectodomain shedding and as a vehicle for the cellular export of soluble molecules.
            Article 0 comments Cited 76 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery.

              Fei Liu, Simona Principe, Thomas Kislinger … (2013)
              Exosomes and microvesicles (MVs) are nanometer-sized, membranous vesicles secreted from many cell types into their surrounding extracellular space and into body fluids. These two classes of extracellular vesicles are regarded as a novel mechanism through which cancer cells, including virally infected cancer cells, regulate their micro-environment via the horizontal transfer of bioactive molecules: proteins, lipids, and nucleic acids (DNA, mRNA, micro-RNAs; oncogenic cargo hence often referred to as oncosomes). In head and neck cancer (HNC), exosomes and MVs have been described in Epstein Barr Virus (EBV)-associated nasopharyngeal cancer (NPC), as well as being positively correlated with oral squamous cell carcinoma (OSCC) progression. It has therefore been suggested that HNC-derived vesicles could represent a useful source for biomarker discovery, enriched in tumor antigens and cargo; hence fundamentally important for cancer progression. This current review offers an overall perspective on the roles of exosomes and MVs in HNC biology, focusing on EBV-associated NPC and OSCC. We also highlight the importance of saliva as a proximal and easily accessible bio-fluid for HNC detection, and propose that salivary vesicles might serve as an alternative model in the discovery of novel HNC biomarkers. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
              Article 0 comments Cited 47 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Mol Cell Oncol
                Journal ID (iso-abbrev): Mol Cell Oncol
                Journal ID (pmc): KMCO
                Title: Molecular & Cellular Oncology
                Publisher: Taylor & Francis
                ISSN (Electronic): 2372-3556
                Publication date Collection: May 2016
                Publication date (Electronic): 30 March 2016
                Volume: 3
                Issue: 3
                Electronic Location Identifier: e975082
                Affiliations
                Ontario Cancer Institute; University Health Network ; Toronto, Canada
                Author notes
                [* ]Correspondence to: Rama Khokha; Email: rkhokha@ 123456uhnres.utoronto.ca
                Article
                Publisher ID: 975082
                DOI: 10.4161/23723556.2014.975082
                PMC ID: 4909426
                PubMed ID: 27314104
                SO-VID: f87aaab5-6a2f-4b7d-ab9b-1387bba476e3
                Copyright © © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                Date received : 14 September 2014
                Date revision received : 21 September 2014
                Date accepted : 22 September 2014
                Page count
                Figures: 1, Tables: 0, References: 10, Pages: 3
                Categories
                Subject: Author's View

                Keywords: adam10,caf,complete timp deficiency,exosomes,notch,rhoa,timp
                Data availability:
                Keywords: adam10, caf, complete timp deficiency, exosomes, notch, rhoa, timp

                Comments

                Comment on this article

                scite_

                Similar content489

                See all similar

                Cited by4

                See all cited by

                Most referenced authors164

                See all reference authors