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.
Mol Med Rep. 2020 May;21(5):2051-2062. doi: 10.3892/mmr.2020.11025. Epub 2020 Mar 12.
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.
间充质干细胞 (MSCs) 影响肿瘤进展的多个方面，如血管生成、肿瘤生长和转移。骨髓间充质干细胞 (BM-MSCs) 是具有多能分化能力的成纤维细胞样细胞，定位于组织损伤区域，包括伤口和实体瘤。抑癌基因 p53 在细胞周期控制、细胞凋亡和基因组稳定性方面具有功能，并且在大多数人类癌症中发生突变和失活。本研究旨在探讨 p53 在 BM-MSCs 生物学中的作用。在本研究中，观察到 p53 野生型 (p53+/+)、敲低 (p53+/−) 和敲除 (p53−/−) 小鼠 BM-MSCs (mBM-MSCs) 在外观和细胞表面标志物表达上相似，但表达不同水平的 p53 蛋白。与源自 p53+/+ 小鼠的 mBM-MSCs 相比，p53+/−和 p53−/−mBM-MSCs 表现出更高的增殖率。来自所有三组的 mBM-MSCs，代表不同的 p53 状态，在体内 3 个月的时间内无法形成肿瘤。在没有 p53 的情况下，mBM-MSCs 的成脂和成骨分化增加。p53+/−和 p53−/−mBM-MSCs 的集落形成和迁移能力显著增强，与 p53+/+ 相比，干细胞相关蛋白的表达水平显著升高。p53+/−和 p53−/−mBM-MSCs 中的 microRNA (miR)-3152 和 miR-337 的表达水平显著升高，而 miR-221、miR-155、miR-1288 和 miR-4669 的表达水平显著降低。p53+/−和 p53−/−mBM-MSCs 上清液中肿瘤坏死因子-α和干扰素-γ诱导蛋白-10 的表达水平显著上调。泛素蛋白连接酶 E3 成分 n-识别蛋白 2、RING 指蛋白 31 和基质金属蛋白酶 19 在 p53+/−和 p53−/−mBM-MSCs 中高度表达。本研究结果表明，p53 可能在 mBM-MSCs 的生物学中发挥重要作用，并可为不同 p53 状态的细胞在癌症进展中的作用提供新的见解。
