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      Microenvironment drug resistance in multiple myeloma: emerging new players

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          Abstract

          Multiple myeloma (MM) drug resistance (DR) is a multistep transformation process based on a powerful interplay between bone marrow stromal cells and MM cells that allows the latter to escape anti-myeloma therapies. Here we present an overview of the role of the bone marrow microenvironment in both soluble factors-mediated drug resistance (SFM-DR) and cell adhesion-mediated drug resistance (CAM-DR), focusing on the role of new players, namely miRNAs, exosomes and cancer-associated fibroblasts.

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          Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis.

          Nobuyoshi Kosaka, Haruhisa Iguchi, Takahiro Ochiya (2010)
          In the past several years, the importance of microRNA (miRNA) in cancer cells has been recognized. Proper control of miRNA expression is essential for maintaining a steady state of the cellular machinery. Recently, it was discovered that extracellular miRNAs circulate in the blood of both healthy and diseased patients, although ribonuclease is present in both plasma and serum. Most of the circulating miRNAs are included in lipid or lipoprotein complexes, such as apoptotic bodies, microvesicles, or exosomes, and are, therefore, highly stable. The existence of circulating miRNAs in the blood of cancer patients has raised the possibility that miRNAs may serve as a novel diagnostic marker. However, the secretory mechanism and biological function, as well as the meaning of the existence of extracellular miRNAs, remain largely unclear. In this review, we summarize the usefulness of circulating miRNA for cancer diagnosis, prognosis, and therapeutics. Furthermore, we propose a mechanism for the secretion and incorporation of miRNA into the cells. © 2010 Japanese Cancer Association.
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            Exosomes: a common pathway for a specialized function.

            Guillaume van Niel, Isabel Porto-Carreiro, Sabrina Simões … (2006)
            Exosomes are membrane vesicles that are released by cells upon fusion of multivesicular bodies with the plasma membrane. Their molecular composition reflects their origin in endosomes as intraluminal vesicles. In addition to a common set of membrane and cytosolic molecules, exosomes harbor unique subsets of proteins linked to cell type-associated functions. Exosome secretion participates in the eradication of obsolete proteins but several findings, essentially in the immune system, indicate that exosomes constitute a potential mode of intercellular communication. Release of exosomes by tumor cells and their implication in the propagation of unconventional pathogens such as prions suggests their participation in pathological situations. These findings open up new therapeutic and diagnostic strategies.
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              Exosomes in cancer: small particle, big player

              Xu Zhang, Xiao Shuai Yuan, Hui Shi … (2015)
              Exosomes have emerged as a novel mode of intercellular communication. Exosomes can shuttle bioactive molecules including proteins, DNA, mRNA, as well as non-coding RNAs from one cell to another, leading to the exchange of genetic information and reprogramming of the recipient cells. Increasing evidence suggests that tumor cells release excessive amount of exosomes, which may influence tumor initiation, growth, progression, metastasis, and drug resistance. In addition, exosomes transfer message from tumor cells to immune cells and stromal cells, contributing to the escape from immune surveillance and the formation of tumor niche. In this review, we highlight the recent advances in the biology of exosomes as cancer communicasomes. We review the multifaceted roles of exosomes, the small secreted particles, in communicating with other cells within tumor microenvironment. Given that exosomes are cell type specific, stable, and accessible from body fluids, exosomes may provide promising biomarkers for cancer diagnosis and represent new targets for cancer therapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncotarget
                Journal ID (iso-abbrev): Oncotarget
                Journal ID (publisher-id): Oncotarget
                Journal ID (publisher-id): ImpactJ
                Title: Oncotarget
                Publisher: Impact Journals LLC
                ISSN (Electronic): 1949-2553
                Publication date Collection: 13 September 2016
                Publication date (Electronic): 26 July 2016
                Volume: 7
                Issue: 37
                Pages: 60698-60711
                Affiliations
                1 Department of Biomedical Sciences and Human Oncology, Internal Medicine Section, University of Bari Medical School, Bari, Italy
                2 Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy
                3 Department of Biomedical Sciences and Human Oncology, General Pathology Section, Bari, Italy
                Author notes
                Correspondence to: Angelo Vacca, angelo.vacca@ 123456uniba.it
                Article
                Publisher ID: 10849
                DOI: 10.18632/oncotarget.10849
                PMC ID: 5312413
                PubMed ID: 27474171
                SO-VID: 396bdabc-f961-41c2-95dd-60fcab155eb8
                Copyright © Copyright: © 2016 Marzo et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 5 May 2016
                Date accepted : 11 July 2016
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer-associated fibroblasts,drug resistance,exosomes,micrornas,multiple myeloma
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cancer-associated fibroblasts, drug resistance, exosomes, micrornas, multiple myeloma

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