Journal of Circulating Biomarkers最新文献_第10页

Rab27B-Mediated Metabolic Reprogramming Induces Secretome Acidification and Chemoresistance in Breast Cancer Cells rab27b介导的代谢重编程诱导乳腺癌细胞分泌组酸化和化疗耐药

Journal of Circulating Biomarkers Pub Date : 2013-01-01 DOI: 10.5772/56521

A. Hendrix, C. Ciccone, C. Gespach, M. Bracke, O. De Wever, W. Westbroek

{"title":"Rab27B-Mediated Metabolic Reprogramming Induces Secretome Acidification and Chemoresistance in Breast Cancer Cells","authors":"A. Hendrix, C. Ciccone, C. Gespach, M. Bracke, O. De Wever, W. Westbroek","doi":"10.5772/56521","DOIUrl":"https://doi.org/10.5772/56521","url":null,"abstract":"The secretory Rab27B small GTPase promotes invasive growth, tumourigenicity and metastasis in oestrogen receptor (ER)-positive human breast cancer cells. Coherently, increased Rab27B expression in breast cancer patients is associated with a poor prognosis. In the present study, bio-energetic profiling revealed that oxidative phosphorylation is significantly reduced in ER-positive breast cancer cells engineered to overexpress Rab27B levels as observed in invasive clinical primary breast cancer. Rab27B-induced metabolic reprogramming to aerobic glycolysis was further evidenced by increased extracellular acidification followed by cathepsin B activation and doxorubicin resistance. Transient silencing of Rab27B and stable transfection of Rab27A, and Rab27B mutants in ER-positive breast cancer cells confirmed that this response was Rab27B-specific and dependent upon Rab27B-GTP activation and vesicle membrane attachment through the C-terminal geranylgeranyl group of this small GTPase. Rab27B-driven extracellular acidification is required and is sufficient to induce filopodia-like morphological changes, primarily involved in the process of cancer cell invasion. Our data demonstrate that a Rab27B-dependent switch from oxidative phosphorylation towards aerobic glycolysis in ER-positive breast cancer cells is accompanied by acidification of the tumour environment.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/56521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70954312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Tumour Cells Incorporate Exosomes Derived from Dendritic Cells through a Mechanism Involving the Tetraspanin CD9 肿瘤细胞通过与四蛋白CD9相关的机制整合来自树突状细胞的外泌体

Journal of Circulating Biomarkers Pub Date : 2013-01-01 DOI: 10.5772/52069

G. Romagnoli, P. A. Toniolo, Isabela Katz Migliori, E. Caldini, M. A. Ferreira, C. R. Pizzo, P. C. Bergami-Santos, J. Barbuto

{"title":"Tumour Cells Incorporate Exosomes Derived from Dendritic Cells through a Mechanism Involving the Tetraspanin CD9","authors":"G. Romagnoli, P. A. Toniolo, Isabela Katz Migliori, E. Caldini, M. A. Ferreira, C. R. Pizzo, P. C. Bergami-Santos, J. Barbuto","doi":"10.5772/52069","DOIUrl":"https://doi.org/10.5772/52069","url":null,"abstract":"Exosomes (Exos) are secreted nanovesicles that contain membrane proteins and genetic material, which can be transferred between cells and contribute to their communication in the body. We show that Exos, obtained from mature human dendritic cells (DCs), are incorporated by tumour cells, which after Exos treatment, acquire the expression of HLA-class I, HLA-class II, CD86, CD11c, CD54 and CD18. This incorporation reaches its peak eight hours after treatment, can be observed in different cell tumour lines (SK-BR-3, U87 and K562) and could be a means to transform non-immunogenic into immunogenic tumour cells. Interestingly, tetraspanins, which are expressed by the tumour cells, have their surface level decreased after Exo treatment. Furthermore, the intensity of Exo incorporation by the different tumour cell lines was proportional to their CD9 expression levels and pre-treatment of Exos with anti-CD9 decreased their incorporation (by SK-BR-3 cells). This modification of tumour cells by DC-derived Exos may allow their use in new immunotherapeutic approaches to cancer. Furthermore, by showing the involvement of CD9 in this incorporation, we provide a possible selection criterion for tumours to be addressed by this strategy.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/52069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70935805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Therapeutic Uses of Exosomes 外泌体的治疗用途

Journal of Circulating Biomarkers Pub Date : 2013-01-01 DOI: 10.5772/56522

Z. Suntres, Milton G. Smith, F. Momen-Heravi, Jie Hu, Xin Zhang, Ying Wu, Hongguang Zhu, Jiping Wang, Jian Zhou, W. Kuo

{"title":"Therapeutic Uses of Exosomes","authors":"Z. Suntres, Milton G. Smith, F. Momen-Heravi, Jie Hu, Xin Zhang, Ying Wu, Hongguang Zhu, Jiping Wang, Jian Zhou, W. Kuo","doi":"10.5772/56522","DOIUrl":"https://doi.org/10.5772/56522","url":null,"abstract":"Exosomes are membrane vesicles with a diameter of 40–100 nm that are secreted by many cell types into the extracellular milieu. Exosomes are found in cell culture supernatants and in different biological fluids and are known to be secreted by most cell types under normal and pathological conditions. Considerable research is focusing on the exploitation of exosomes in biological fluids for biomarkers in the diagnosis of disease. More recently, exosomes are being exploited for their therapeutic potential. Exosomes derived from dendritic cells, tumor cells, and malignant effusions demonstrate immunomodulatory functions and are able to present antigens to T-cells and stimulate antigen-specific T-cell responses. Exosomes have also been examined for their therapeutic potential in the treatment of infections such as toxoplasmosis, diphtheria, tuberculosis and atypical severe acute respiratory syndrome as well as autoimmune diseases. Attempts to find practical applications for exosomes continue to expand with the role of exosomes as a drug delivery system for the treatment of autoimmune/inflammatory diseases and cancers.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/56522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70954411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32

Exosome: A Novel and Safer Therapeutic Refinement of Mesenchymal Stem Cell 外泌体:一种新的、更安全的间充质干细胞治疗方法

Journal of Circulating Biomarkers Pub Date : 2013-01-01 DOI: 10.5772/57460

R. Yeo, R. C. Lai, K. Tan, S. Lim

引用次数: 50

Ovarian Cancer-Derived Exosomal Fibronectin Induces Pro-Inflammatory IL-1β 卵巢癌源性外泌体纤维连接蛋白诱导促炎性IL-1β

Journal of Circulating Biomarkers Pub Date : 2013-01-01 DOI: 10.5772/56180

S. Atay, Carolyn D. Roberson, Ç. Gerçel-Taylor, D. Taylor

{"title":"Ovarian Cancer-Derived Exosomal Fibronectin Induces Pro-Inflammatory IL-1β","authors":"S. Atay, Carolyn D. Roberson, Ç. Gerçel-Taylor, D. Taylor","doi":"10.5772/56180","DOIUrl":"https://doi.org/10.5772/56180","url":null,"abstract":"The tumour microenvironment is characterized by pro-inflammatory profiles, including interleukin-1β (IL-1β). This profile is generated by infiltrating macrophages following interactions with tumours or their components. The objectives of this study were to identify whether tumour exosomes could induce macrophage IL-1β production and the mechanism involved. Exosomes were isolated from ovarian cancer patients and ovarian tumour cells by chromatography and ultracentrifugation. Specific exosomal proteins were defined by mass spectrometry (MS) and confirmed by Western immunoblotting. Using macrophage-like THP-1 cells, induction of IL-1β release was investigated by ELISA. RGD peptides were used to block fibronectin binding by THP-1 α5β1 integrin. Exosomes isolated from ovarian cancer patients and from ovarian cancer cells were demonstrated, by MS and immunoblotting, to express fibronectin. Incubation of THP-1 cells with these exosomes induced pro-inflammatory cytokines, in particular IL-1β. Blocking of THP-1 binding of exosomal fibronectin with RGD peptides abrogated exosome-mediated IL-1β production and down-stream phosphorylation of Akt and c-Jun. Although cancer patients generally exhibit increased levels of IL-1β, the underlying mechanism is unclear. Here, tumour-derived exosomes are demonstrated to induce pro-inflammatory cytokine in macrophages including IL-1β, whose induction is mediated by fibronectin.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/56180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70951424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8