Dataset Information

Proteomic analysis of extracellular vesicles derived from Merkel cell carcinoma cell lines

ABSTRACT: Exosomes constitute an evolutionary conserved mechanism of intercellular signaling. Their importance are gaining increasing such as prognostic and diagnostic markers, and potential therapeutic tool. Merkel cell carcinoma (MCC) is an aggressive form of skin cancer with a poor prognosis. There are not available an effective systemic treatment for this type of cancer, and exosome-based therapy was proposed. We identified with high confident 164 exosome-derived proteins that were common for all four cell lines, which were annotated in ExoCarta and Vesiclepedia databases. This list includes proteins implicated in motility, metastasis and tumor progression.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

SUBMITTER: Jack-Ansgar Bruun

LAB HEAD: Ugo Moens

PROVIDER: PXD004198 | Pride | 2016-08-08

REPOSITORIES: Pride

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Publications

Secretomic analysis of extracellular vesicles originating from polyomavirus-negative and polyomavirus-positive Merkel cell carcinoma cell lines.

Konstantinell Aelita A Bruun Jack-Ansgar JA Olsen Randi R Aspar Augusta A Škalko-Basnet Nataša N Sveinbjørnsson Baldur B Moens Ugo U

Proteomics 20160905 19

Extracellular vesicles or exosomes constitute an evolutionarily conserved mechanism of intercellular signaling. Exosomes are gaining an increasing amount of attention due to their role in pathologies, including malignancy, their importance as prognostic and diagnostic markers, and their potential as a therapeutic tool. Merkel cell carcinoma (MCC) is an aggressive form of skin cancer with a poor prognosis. Because an effective systemic treatment for this cancer type is currently not available, an ...[more]

PMID: 27402257

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Project description:Background: Docosahexaenoic acid (DHA) is a natural compound with anticancer and anti-angiogenesis activity that is currently under investigation as both a preventative agent and an adjuvant to breast cancer therapy. However, the precise mechanisms of DHA’s anticancer activities are unclear. It is understood that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are extracellular vesicles that are important mediators of intercellular communication and play a role in promoting angiogenesis. However, very little is known about the contribution of breast cancer exosomes to tumor angiogenesis or whether exosomes can mediate DHA’s anticancer action. Results: Exosomes were collected from MCF7 and MDA-MB-231 breast cancer cells after treatment with DHA. We observed an increase in exosome secretion and exosome microRNA contents from the DHA-treated cells. The expression of 83 microRNAs in the MCF7 exosomes was altered by DHA (>2-fold). The most abundant exosome microRNAs (let-7a, miR-23b, miR-27a/b, miR-21, let-7, and miR-320b) are known to have anti-cancer and/or anti-angiogenic activity. These microRNAs were also increased by DHA treatment in the exosomes from other breast cancer lines (MDA-MB-231, ZR751 and BT20), but not in exosomes from normal breast cells (MCF10A). When DHA-treated MCF7 cells were co-cultured with or their exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in the endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, suggesting that the microRNAs transferred by exosomes mediate DHA’s anti-angiogenic action. These effects could be reversed by knockdown of the Rab GTPase, Rab27A, which controls exosome release. Conclusions: We conclude that DHA alters breast cancer exosome secretion and microRNA contents, which leads to the inhibition of angiogenesis. Our data demonstrate that breast cancer exosome signaling can be targeted to inhibit tumor angiogenesis and provide new insight into DHA’s anticancer action, further supporting its use in cancer therapy. Examination of small RNA populations in MCF7 cells and exosomes after DHA treatment.

Dataset Information

Proteomic analysis of extracellular vesicles derived from Merkel cell carcinoma cell lines

Publications

Secretomic analysis of extracellular vesicles originating from polyomavirus-negative and polyomavirus-positive Merkel cell carcinoma cell lines.

Similar Datasets

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