Concise Review: Crosstalk of Mesenchymal Stroma/Stem‐Like Cells with Cancer Cells Provides Therapeutic Potential. (16th April 2018)

• Record Type: Journal Article
• Authors: Melzer, Catharina; von der Ohe, Juliane; Hass, Ralf
• Is Part Of: Stem cells. Volume 36:Number 7(2018)
• Page Start: 951
• Page End: 968
• Publication Date: 2018-04-16
• Subjects: Mesenchymal stroma/stem‐like cells -- Cancer cells -- Fusion -- Hybrid cells -- Intercellular communication -- Exosomes -- Microvesicles -- Trogocytosis -- Retrodifferentiation -- Tumor therapy; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2829
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Various direct and indirect cellular interactions between multi‐functional mesenchymal stroma/stem‐like cells (MSCs) and cancer cells contribute to increasing plasticity within the tumor tissue and its microenvironment. Direct and tight communication between MSC and cancer cells is based on membrane protein interactions and the exchange of large plasma membrane fragments also known as trogocytosis. An ultimate but rare direct interaction resumes in fusion of these two cellular partners resulting in the formation of new cancer hybrid cell populations. Alternatively, indirect interactions are displayed by the release of membranous vesicle‐encapsulated microRNAs and proteins or soluble components such as molecular growth factors, hormones, chemo‐/cytokines, and metabolites. Released single molecules as well as multivesicular bodies including exosomes and microvesicles can form local concentration gradients within the tumor microenvironment and are incorporated not only by adjacent neighboring cells but also affect distant target cells. The present Review will focus on vesicle‐mediated indirect communication and on cancer cell fusion with direct contact between MSC and cancer cells. These different types of interaction are accompanied by functional interference and mutual acquisition of new cellular properties. Consequently, alterations in cancer cell functionalities paralleled by the capability to reorganize the tumor stroma can trigger changes in metastatic behavior and promote retrodifferentiation to develop new cancer stem‐like cells. However, exosomes and microvesicles acting over long distances may also provide a tool with therapeutic potential when loaded with anti‐tumor cargo. Stem Cells 2018;36:951–968 Abstract : Mutual indirect cellular interactions between MSC and tumor cells involve the exchange of extracellular vesicles (exosomes, microvesicles, DAMPs, apoptotic bodies, phagosomes) and soluble molecules (cytokines, chemokines, growth factors, peptides, metabolites, ions). Moreover, direct communication between MSC and cancer cells involve membrane protein interactions such as integrin and/or notch signaling, GJIC, trogocytosis and eventually heterofusion resulting in the formation of cancer hybrid cells with altered phenotypes and properties. Such crosstalk affects tumor progression and on the other hand induces differentiation and clonal selection of MSC subpopulations exhibiting an alternating balance between cancer‐promoting (CA + ‐MSC) and cancer‐inhibiting (CA − ‐MSC) properties. The resulting increase in tumor heterogeneity and diversity contributes to ECM restructure, EMT, metastasis, and an appropriate environment for a CSC niche. However, MSC‐derived exosomes represent a supportive vehicle for drug delivery. Moreover, tumor‐targeted extracellular vesicles containing anti‐tumor cargo may provide a promising therapeutic tool carrying biocompatible characteristics.