Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics

Wang,Bo; Wang,Lingxia; Mao,Jiahui; Wen,Huiyan; Xu,Longjiang; Ren,Yang; Du,Hong; Yang,Huan

doi:10.3892/mmr.2020.11025

Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics

Authors:
- Bo Wang
- Lingxia Wang
- Jiahui Mao
- Huiyan Wen
- Longjiang Xu
- Yang Ren
- Hong Du
- Huan Yang
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Affiliations: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
Published online on: March 12, 2020 https://doi.org/10.3892/mmr.2020.11025
Pages: 2051-2062
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mesenchymal stem cells (MSCs) affect diverse aspects of tumor progression, such as angiogenesis, tumor growth and metastasis. Bone marrow MSCs (BM‑MSCs) are fibroblast‑like cells with multipotent differentiation ability, that localize to areas of tissue damage, including wounds and solid tumors. The tumor suppressor gene, p53, is functionally involved in cell cycle control, apoptosis and genomic stability, and is mutated and inactivated in most human cancers. The present study aimed to investigate the role of p53 in the biology of BM‑MSCs. In the present study, p53 wild‑type (p53+/+), knockdown (p53+/‑) and knockout (p53‑/‑) mouse BM‑MSCs (mBM‑MSCs) were observed to be similar in appearance and in the expression of cell surface biomarkers, but expressed differential p53 protein levels. The p53+/‑ and p53‑/‑ mBM‑MSCs demonstrated an increased proliferation rate compared with mBM‑MSCs derived from p53+/+ mice. mBM‑MSCs from all three groups, representing distinct p53 statuses, were unable to form tumors over a 3‑month period in vivo. The adipogenic and osteogenic differentiation of mBM‑MSCs was increased in the absence of p53. The colony formation and migratory abilities of p53+/‑ and p53‑/‑ mBM‑MSCs were markedly enhanced, and the expression levels of stem cell‑associated proteins were significantly increased compared with p53+/+. The expression levels of microRNA (miR)‑3152 and miR‑337 were significantly increased in p53+/‑ and p53‑/‑ mBM‑MSCs, whereas the expression levels of miR‑221, miR‑155, miR‑1288 and miR‑4669 were significantly decreased. The expression levels of tumor necrosis factor‑α and interferon‑γ‑inducible protein‑10 were significantly upregulated in the supernatant of p53+/‑ and p53‑/‑ mBM‑MSCs. Ubiquitin protein ligase E3 component n‑recognin 2, RING‑finger protein 31 and matrix metalloproteinase 19 were highly expressed in p53+/‑ and p53‑/‑ mBM‑MSCs. The results of the present study indicated that p53 may serve an important role in the biology of mBM‑MSCs, and may provide novel insights into the role of cells with different p53 statuses in cancer progression.

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