Clinical implications of microRNAs in human glioblastoma

Mizoguchi, Masahiro; Guan, Yanlei; Yoshimoto, Koji; Hata, Nobuhiro; Amano, Toshiyuki; Nakamizo, Akira; Sasaki, Tatsuya

doi:10.3389/fonc.2013.00019

Cited by 51 publications

(46 citation statements)

References 65 publications

(93 reference statements)

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“…Previous studies have revealed that tumor cells are a dynamic resource for exosomes, such as melanoma (20), prostate cancer (21) and gliobastoma (22). Exosomes have been detected in human malignant effusions (12).…”

Section: Discussionmentioning

confidence: 99%

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The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10

Wang

Chen

et al. 2015

Oncology Letters

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Abstract. Tumorigenesis has been considered to be as a result of abnormal cell-cell communication. It has been proposed that exosomes act as communicators between tumors and their microenvironment and have been demonstrated to be involved in tumorigenesis and subsequent metastasis. However, the mechanisms underlying the role of exosomes in these processes remains elusive. The present study sought to determine the underlying mechanisms. Using two lung cancer cell lines, it was demonstrated that exosomes derived from metastatic small cell lung cancer cells (NCI-H1688) have greater effects on cancer cell migration, compared with exosomes derived from primary non-small cell lung cancer cells (NCI-H2228). Further characterization of the contents of the exosomes demonstrated that there were increased levels of TGF-β and IL-10 in exosomes from NCI-H1688 cells compared with exosomes derived from NCI-H2228 cells, in particular under hypoxia. Blockade of TGF-β and IL-10 with antibodies confirmed that these cytokines were essential for the regulation of cancer cell migration. Taken together, the results of the present study indicated that exosomes derived from cancer cells regulated the cellular migration of tumor cells through TGF-β and IL-10, which may provide a novel approach for developing therapeutic methods against cancer.

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Section: Discussionmentioning

confidence: 99%

“…A number of miRs have been demonstrated to be present in exosomes from various cells (including cancer cells), which serve essential roles in the regulation of tumor cell migration (21)(22)(23)(24)(25)(26)(27). Other miRs may be involved in other steps of tumor development: miR-31, -185, and -34b are involved in melanoma invasion (25).…”

Section: Discussionmentioning

confidence: 99%

The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10

Wang

Chen

et al. 2015

Oncology Letters

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“…In a Drosophilia model, exosomes have been shown to induce miRNA splicing [138]. In later studies, a number of groups have proposed to use exosomal miRNAs for diagnostic and prognostic purposes for several cancers such as breast [139], lung [140], colon [141], esophageal squamous cell carcinoma [142], glioblastoma [143], kidney [144], leukemia [145], ovarian [146], prostate [147,148], and for other cancers [149].…”

Section: Liquid Biopsies-the Future?mentioning

confidence: 99%

Challenges and Strategies in Precision Medicine for Non-Small-Cell Lung Cancer

Sacco

Al‐Akhrass²,

Wilson

2016

CPD

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Lung cancer is the most common cause of cancer-related death worldwide, causing over 1.2 million deaths each year. Non-small-cell lung cancer (NSCLC) consists of a group of malignancies that are pathologically and molecularly diverse but that are all characterised by a poor prognosis. Survival rates for lung cancer patients have improved very slowly and only to a modest degree owing partly to poor funding for research into this malignancy and stigma associated with smoking, as well as relative chemo-resistance. However, in recent years, NSCLC has become an exemplar for precision medicine, mainly following development of drugs targeting the receptors of epidermal growth factor and anaplastic lymphoma kinase. While epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors are only applicable to a minority of patients and benefits are almost invariably short-lived, current studies indicate that at least 50% of patients with NSCLC have a targetable mutation. With a growing armamentarium of inhibitors against these targets in development, there is a hope that a greater proportion of patients will benefit from precision medicine and that such benefits will be sustained. However, there remain significant challenges in the development of precision medicine in NSCLC. These include: identification and validation of new targets; ensuring biopsies are fit for purpose; tumour heterogeneity; requirements for serial tumour assessments; and not least cost. In this review, we will discuss the current status of precision medicine in NSCLC as well as how basic and translational research are paving the way towards overcoming the above challenges. In addition, we will pay attention to clinical

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“…The essential roles of exosomes have been demonstrated in a number of studies conducted in various tumor types, such as prostate cancer, and melanoma (9,11,12). Exosomes derived from different types of cancer contain different combinations of biological molecules, and have distinctive effects on tumor behavior.…”

Section: Introductionmentioning

confidence: 99%

“…Exosomes derived from different types of cancer contain different combinations of biological molecules, and have distinctive effects on tumor behavior. Many miRNAs have been discovered in exosomes from tumor cells and stroma cells, which are essential in the regulation of tumor cell migration (9,10,(12)(13)(14)(15)(16). Certain miRNAs may be involved in multiple stages of tumor development; for example, miR-31, -185, and -34b are involved in melanoma invasion (10).…”

Section: Introductionmentioning

confidence: 99%

Immunosuppression of breast cancer cells mediated by transforming growth factor-β in exosomes from cancer cells

Rong

et al. 2015

Oncology Letters

132

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Abstract. Exosomes derived from tumor cells are essential for processes involved in tumor progression, including angiogenesis, tumor cell proliferation and immunoregulation. In addition, exosome secretion may contribute to the mechanisms of hypoxia-induced angiogenesis and metastasis of tumors. In the present study, as it is one of the most common cancers in females, breast cancer, cell lines were cultured under hypoxic (1% O 2 ) and normoxic conditions to evaluate the effects of hypoxia on exosome production. Under hypoxic conditions an increase in the number of exosomes in the medium, determined by CD63 immunoblotting, was observed. Application of these exosomes to T cells revealed that they were able to suppress T cell proliferation. As transforming growth factor-β (TGF-β), interleukin-10, and prostaglandin E2 are important factors in the mediation of T cell suppression, the exosomes were subsequently treated with antibodies against these three factors. The results revealed that anti-TGF-β was capable of ameliorating the immunosuppressive effects of exosomes. These data demonstrate that hypoxia enhances the secretion of exosomes by breast cancer cells, which acts to suppress T cell proliferation via TGF-β. The findings have significant implications for understanding the underlying mechanisms of immunosuppression in tumor microenvironments, and for the potential development of cancer therapies.

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Clinical implications of microRNAs in human glioblastoma

Cited by 51 publications

References 65 publications

The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10

The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10

Challenges and Strategies in Precision Medicine for Non-Small-Cell Lung Cancer

Immunosuppression of breast cancer cells mediated by transforming growth factor-β in exosomes from cancer cells

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