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

Mesenchymal stem cells (MSCs) affect diverse aspects of tumor progression, such as angiogenesis, tumor growth and metastasis. Bone marrow MSCs (BMMSCs) are fibroblastlike 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 BMMSCs. In the present study, p53 wildtype (p53+/+), knockdown (p53+/) and knockout (p53/) mouse BMMSCs (mBMMSCs) 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/ mBMMSCs demonstrated an increased proliferation rate compared with mBMMSCs derived from p53+/+ mice. mBMMSCs from all three groups, representing distinct p53 statuses, were unable to form tumors over a 3month period in vivo. The adipogenic and osteogenic differentiation of mBMMSCs was increased in the absence of p53. The colony formation and migratory abilities of p53+/ and p53/ mBMMSCs were markedly enhanced, and the expression levels of stem cellassociated proteins were significantly increased compared with p53+/+. The expression levels of microRNA (miR)3152 and miR337 were significantly increased in p53+/ and p53/ mBMMSCs, whereas the expression levels of miR221, miR155, miR1288 and miR4669 were significantly decreased. The expression levels of tumor necrosis factoralpha and interferongammainducible protein10 were significantly upregulated in the supernatant of p53+/ and p53/ mBMMSCs. Ubiquitin protein ligase E3 component nrecognin 2, RINGfinger protein 31 and matrix metalloproteinase 19 were highly expressed in p53+/ and p53/ mBMMSCs. The results of the present study indicated that p53 may serve an important role in the biology of mBMMSCs, and may provide novel insights into the role of cells with different p53 statuses in cancer progression.