Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

Melo, Sônia Aparecida Beato Ximenes de; Sugimoto, Hikaru; O’Connell, Joyce T.; Kato, Noritoshi; Villanueva, Alberto; Vidal, August; Qiu, Le; Vitkin, Edward; Perelman, Lev T.; Melo, Carlos A.; Lucci, Anthony; Ivan, Cristina; Calin, George A.; Kalluri, Raghu

doi:10.1016/j.ccell.2014.09.005

Cited by 1,350 publications

(1,213 citation statements)

References 58 publications

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“…Melo et al indicated that TEXs promoted tumorigenesis by modulating cell-independent miRNAs biogenesis. 13 Exosomes from breast cancer cells contained miRNAs associated with the RNA-induced silencing complex (RISC), Dicer, TAR RNA-binding protein 2 (TRBP) and Argonaute-2 (AGO2). When transferred to recipient cells, the exosomes could efficiently silence mRNA expression and thereby instigate non-tumorigenic epithelial cells to form tumors in a Dicer-dependent manner.…”

Section: Overview Of Exosomes In Cancer Progressionmentioning

confidence: 99%

The exosomes in tumor immunity

2015

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Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4 C and CD8 C T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4 C and CD8 C Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DCderived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.

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Section: Overview Of Exosomes In Cancer Progressionmentioning

confidence: 99%

The exosomes in tumor immunity

2015

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“…However, the mechanisms of luminal filling initiation are poorly understood. Recent studies have reported that carcinoma cells directly contact normal epithelial cells through filopodia-like projections in the 3D co-culture system, or they secrete MMP-9 that cleaves E-cadherin disrupting the luminal architecture [28], or alternatively they use exosomes to induce oncogenic transformation of adjacent normal epithelial cells [29]. Our results were consistent with previous reports, and we went a step further and compared the properties of C2 and C3 cancer cells and found that the transmitted cancer cells (C2 cells) were more malignant than the original cancer cells (C3 cells), which could explain how cancer heterogeneity is formed.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic transformation of normal breast epithelial cells co-cultured with cancer cells

Song

Zhou

et al. 2018

Cell Cycle

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The heterogeneity in human breast cancer poses a challenge for effective treatment. Better understanding of tumor initiation and development will help to resolve this problem. Current models explaining intratumoral diversity include cancer stem cells, clonal evolution and cancer cell dedifferentiation and reprogramming. Herein, a new model, cancer transmission, is proposed to explain cancer heterogeneity. We found breast cancer cells (MCF10A.NeuT) were capable of transforming normal mammary epithelial cells (MCF10A). The transformed cells exhibited cancerous properties including enhanced proliferation and migration, loss of apical-basal polarity and depolarized acini structure associated with epithelial-mesenchymal transition (EMT). The transformed MCF10A cells displayed distinct EMT characteristics compared to parental cells. We further showed that cancer cell-secreted factors were sufficient to induce cancerous transformation of normal cells. Furthermore, transformed cells were resistant to radiation treatment, providing new insights into mechanisms underlying therapeutic resistance.

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“…These small non-coding RNAs plays important roles in cancer, 76 explaining why this discovery suggested a new regulatory role for exosomes in cancer. Today, numerous studies have identified different functional exosomal miRNAs and their role in cancer, 77,78 and proposed their use as diagnosis biomarkers. 79,80,81 For example, in lung cancer 2 miRNAs, miR-21 and miR-155 have been found to be significantly upregulated in recurrent tumors compared to primary tumors.…”

Section: Exosomes As Biomarkersmentioning

confidence: 99%

Exosomes in cancer theranostic: Diamonds in the rough

Cordonnier

Chanteloup

Isambert

et al. 2017

Cell Adhesion & Migration

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During the last 10 years, exosomes, which are small vesicles of 50-200 nm diameter of endosomal origin, have aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. Most cells can potentially release these nanovesicles that share with the parent cell a similar lipid bilayer with transmembrane proteins and a panel of enclosed soluble proteins such as heat shock proteins and genetic material, thus acting as potential nanoshuttles of biomarkers. Exosomes surface proteins allow their targeting and capture by recipient cells, while the exosomes' content can modify the physiological state of recipient cells. Tumor derived exosomes by interacting with other cells of the tumor microenvironment modulate tumor progression, angiogenic switch, metastasis, and immune escape. Targeting tumor-derived exosomes might be an interesting approach in cancer therapy. Furthermore, because a key issue to improve cancer patients' outcome relies on earlier cancer diagnosis (metastases, as opposed to the primary tumor, are responsible for most cancer deaths) exosomes have been put forward as promising biomarker candidates for cancer diagnosis and prognosis. This review summarizes the roles of exosomes in cancer and clinical interest, focusing on the importance of exosomal heat shock proteins (HSP). The challenges of clinical translation of HSPexosomes as therapeutic targets and biomarkers for early cancer detection are also discussed.

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Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

Cited by 1,350 publications

References 58 publications

The exosomes in tumor immunity

The exosomes in tumor immunity

Oncogenic transformation of normal breast epithelial cells co-cultured with cancer cells

Exosomes in cancer theranostic: Diamonds in the rough

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