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.
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 (MDA MB 231) cancer cells in vitro. Both WJ-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 in WHCO1 and MDA 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.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), UCT Campus, Anzio Road, Observatory, Cape Town 7925, South Africa; Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
authors.forename: Kevin
authors.initials: K
authors.lastname: Dzobo
authors.affiliation: Perlmutter Cancer Centre, New York University, School of Medicine, New York, NY 10016, USA.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Vogelsang
authors.affiliation: Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Thomford
authors.affiliation: Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
authors.affiliation: Department of Immunology and Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Gezina, Pretoria 0002, South Africa.
authors.forename: Karlien
authors.initials: K
authors.lastname: Kallmeyer
authors.affiliation: Department of Immunology and Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Gezina, Pretoria 0002, South Africa.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Pepper
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), UCT Campus, Anzio Road, Observatory, Cape Town 7925, South Africa; Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South Africa.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Parker