Dataset Information

Human mesenchimal stem cells secretome

ABSTRACT: The study reports for the first time a quantitative proteomic characterization of the secretome of human bone marrow derived MSC before and after stimulation with a panel of pro-inflammatory cytokines.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

SUBMITTER: gabriella tedeschi

LAB HEAD: Gabriella Tedeschi

PROVIDER: PXD005746 | Pride | 2017-08-11

REPOSITORIES: Pride

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Publications

Proteomic analysis of the secretome of human bone marrow-derived mesenchymal stem cells primed by pro-inflammatory cytokines.

Maffioli Elisa E Nonnis Simona S Angioni Roberta R Santagata Fabiana F Calì Bianca B Zanotti Lucia L Negri Armando A Viola Antonella A Tedeschi Gabriella G

Journal of proteomics 20170721

Mesenchymal stem cells (MSC) represent an impressive opportunity in term of regenerative medicine and immunosuppressive therapy. Although it is clear that upon transplantation MSC exert most of their therapeutic effects through the secretion of bioactive molecules, the effects of a pro-inflammatory recipient environment on MSC secretome have not been characterized. In this study, we used a label free mass spectrometry based quantitative proteomic approach to analyze how pro-inflammatory cytokine ...[more]

PMID: 28739509

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Project description:Iron is required as a cofactor for many critical cellular enzymes involved in energy metabolism and cell proliferation and is thus essential for all living cells. To facilitate the rapid replication, the neoplastic cells have significantly higher levels of ribonucleotide reductase and the transferrin receptor 1 (TfR1) and many in vitro and in vivo studies have demonstrated that, compared to normal cells, cancer cells are more sensitive to iron (Fe) deprivation because of their marked Fe requirements. The higher Fe utilization by cancer cells provides a rationale for the selective antitumor activity of chelators. To date, Deferoxamine (DFO) is one of the most widely used iron chelator. In addition, DFO also has some antitumor activity. Moreover, novel chelators based on the di-2-pyridylketone thiosemicarbazone (DpT) scaffold, such as di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), induce iron sequestration and also form redox-active metal complexes that demonstrate potent and selective anti-tumor activity. Notably, Dp44mT and its analogs possess broad anti-cancer and anti-metastatic activity in vitro and in vivo against a variety of aggressive solid tumors. Understanding the mechanism of action of these ligands and their effect on the ER stress pathway will yield better clinical outcomes. It has been reported that iron depletion induced by Dp44mT and its metal complexes causes apoptosis by generating cytotoxic ROS and by inducing DNA strand breaks. The redox active complexes formed in lysosomes induce damages generating tumor cell cytotoxicity. The alterations in gene expression after iron depletion are complex. Moreover, in cultured cells Dp44mT resulted in marked up-regulation of the Fe-responsive tumor growth and metastasis suppressor Ndrg1 (N-myc downstream regulated gene-1). Therefore, Up-regulation of Ndrg1 may be another mechanism by which chelators inhibit cancer cell proliferation. Here we combine biochemistry, microscopy, flow cytometry and LC/MS-MS analyses to investigate cellular events induced by DFO and Dp44mT iron chelators on two human breast cancer cell lines, MDA-MB-231 and MDA-MB-157, in terms of proliferation, cell cycle, cytotoxicity and death. These experiments could potentially provide additional information in terms of the mechanism(s) of action of iron chelators in breast cancer cells.

Dataset Information

Human mesenchimal stem cells secretome

Publications

Proteomic analysis of the secretome of human bone marrow-derived mesenchymal stem cells primed by pro-inflammatory cytokines.

Similar Datasets

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