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
Kevin DzoboM Iqbal Parker

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.

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Citations

Dec 9, 2016·Omics : a Journal of Integrative Biology·Kevin DzoboM Iqbal Parker
Dec 21, 2018·Omics : a Journal of Integrative Biology·Kevin DzoboM Iqbal Parker
Apr 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kevin DzoboCollet Dandara
Sep 23, 2018·International Journal of Molecular Sciences·Dimakatso Alice SenthebaneKevin Dzobo
Jul 30, 2017·International Journal of Molecular Sciences·Dimakatso Alice SenthebaneKevin Dzobo
Jan 31, 2019·International Journal of Molecular Sciences·Cheng TianQiong Xu
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Yanghong NiXuelei Ma

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Methods Mentioned

BETA
MDA
flow cytometry
biopsy
electrophoresis
PCR
Transfection
transfections

Software Mentioned

CellQuest
ModFit
GraphPad Prism

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