Wharton’s jelly-derived mesenchymal stromal cells and fibroblast-derived extracellular matrix synergistically activate apoptosis in a p21-dependent mechanism in WHCO1 and MDA MB 231 cancer cells in vitro

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dc.contributor.author Dzobo, Kevin
dc.contributor.author Vogelsang, Matjaz
dc.contributor.author Thomford, Nicholas E.
dc.contributor.author Dandara, Collet
dc.contributor.author Kallmeyer, Karlien
dc.contributor.author Pepper, Michael Sean
dc.contributor.author Parker, M. Iqbal
dc.date.accessioned 2016-08-18T06:58:35Z
dc.date.available 2016-08-18T06:58:35Z
dc.date.issued 2016
dc.description.abstract The tumour microenvironment plays a crucial role in tumour progression and comprises tumour stroma which is made up of different cell types and the extracellular matrix (ECM).Mesenchymal stromal cells (MSCs) are part of the tumour stroma and may have conflicting effects on tumour growth. In this study we investigated the effect of Wharton’s Jelly-derived MSCs (WJ-MSCs) and a fibroblast-derived ECM (fd-ECM) on esophageal (WHCO1) and breast (MDAMB 231) cancer cells in vitro. BothWJ-MSCs and the fd-ECM, alone or in combination, downregulate PCNA, cyclin D1, Bcl-2, Bcl-xL, and MMPs and upregulate p53 and p21. p21 induction resulted in G2 phase cell cycle arrest and induced apoptosis in vitro. Our data suggest that p21 induction is via p53- dependent and p53-independent mechanisms inWHCO1 andMDA MB 231 cells, respectively. Vascular endothelial growth factor, Akt, and Nodal pathways were downregulated in cancer cells cocultured with WJ-MSCs. We also demonstrate that WJ-MSCs effects on cancer cells appear to be short-lived whilst the fd-ECM effect is long-lived. This study shows the influence of tumour microenvironment on cancer cell behaviour and provides alternative therapeutic targets for potential regulation of tumour cells. en_ZA
dc.description.department Immunology en_ZA
dc.description.librarian am2016 en_ZA
dc.description.sponsorship The International Centre for Genetic Engineering and Biotechnology (ICGEB), the South African Medical Research Council, the National Research Foundation (NRF) of South Africa, theUniversity of Pretoria, and the University of Cape Town. Karlien Kallmeyer and Michael S. Pepper’s work was funded by the South African Medical Research Council (University Flagship award and Extramural Stem Cell Unit). en_ZA
dc.description.uri http://www.hindawi.com/journals/sci/ en_ZA
dc.identifier.citation Dzobo, K, Vogelsang, M, Thomford, NE, Dandara, C, Kallmeyer, K, Pepper, MS & Parker, MI 2016, 'Wharton’s jelly-derived mesenchymal stromal cells and fibroblast-derived extracellular matrix synergistically activate apoptosis in a p21-dependent mechanism in WHCO1 and MDA MB 231 cancer cells in vitro', Stem Cells International, vol. 2016, pp. 1-17. en_ZA
dc.identifier.issn 1687-966X (print)
dc.identifier.issn 1687-9678 (online)
dc.identifier.other 10.1155/2016/4842134
dc.identifier.uri http://hdl.handle.net/2263/56389
dc.language.iso en en_ZA
dc.publisher Hindawi Publishing Corporation en_ZA
dc.rights © 2016 Kevin Dzobo et al.This is an open access article distributed under the Creative Commons Attribution License. en_ZA
dc.subject Tumour microenvironment en_ZA
dc.subject In vitro en_ZA
dc.subject Tumour cells en_ZA
dc.subject Extracellular matrix (ECM) en_ZA
dc.subject Mesenchymal stromal/stem cells (MSCs) en_ZA
dc.subject Wharton’s Jelly-derived MSCs (WJ-MSCs) en_ZA
dc.subject Fibroblast-derived ECM (fd-ECM) en_ZA
dc.subject Esophageal (WHCO1) en_ZA
dc.subject Breast (MDAMB 231) en_ZA
dc.subject Cancer cells en_ZA
dc.title Wharton’s jelly-derived mesenchymal stromal cells and fibroblast-derived extracellular matrix synergistically activate apoptosis in a p21-dependent mechanism in WHCO1 and MDA MB 231 cancer cells in vitro en_ZA
dc.type Article en_ZA


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