Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation

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dc.contributor.authorHogan, Niamh M.en
dc.contributor.authorJoyce, Myles R.en
dc.contributor.authorMurphy, J. Maryen
dc.contributor.authoret al.en Elsevieren
dc.identifier.citationBiochemical and Biophysical Research Communicationsen
dc.description.abstractMesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs + antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively. Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67–88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels. This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the significant functional impact of Mesenchymal Stem Cell-secreted PAI-1 on colon cancer cells.en
dc.rightsThis is the author's version of a work that was accepted for publication in Biochemical and Biophysical Research Communications. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochemical and Biophysical Research Communications (435, 4, (2013)) DOI: http://dx.doi/org/10.1016/j.bbrc.2013.05.013en
dc.subjectMesenchymal Stem Cellen
dc.subjectColorectal canceren
dc.subjectPlasminogen activator inhibitor type 1en
dc.titleImpact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferationen
dc.typeJournal Articleen
dc.internal.availabilityFull text availableen
dc.statusPeer revieweden
dc.neeo.contributorHogan|Niamh M.|aut|-
dc.neeo.contributorJoyce|Myles R.|aut|-
dc.neeo.contributorMurphy|J. Mary|aut|-
dc.neeo.contributoret al.||aut|-
dc.description.adminDeposited by bulk importen
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