Department of Internal Medicine, Molecular Biotechnology Center, University of Torino, Torino, Italy.
Stem Cells Dev. 2013 Mar 1;22(5):758-71. doi: 10.1089/scd.2012.0304. Epub 2012 Nov 19.
Mesenchymal stem cells (MSCs) have opposite effects on tumor growth, being able either to favor angiogenesis and tumor initiation or to inhibit progression of established tumors. Factors produced by MSCs within the tumor microenvironment may be relevant for their biological effects. Recent studies demonstrated that microvesicles (MVs) are an integral component of inter-cellular communication within the tumor microenvironment. In the present study, we evaluated whether MVs derived from human bone marrow MSCs may stimulate or inhibit in vitro and in vivo growth of HepG2 hepatoma, Kaposi's sarcoma, and Skov-3 ovarian tumor cell lines. We found that MVs inhibited cell cycle progression in all cell lines and induced apoptosis in HepG2 and Kaposi's cells and necrosis in Skov-3. The observed activation of negative regulators of cell cycle may explain these biological effects. In vivo intra-tumor administration of MVs in established tumors generated by subcutaneous injection of these cell lines in SCID mice significantly inhibited tumor growth. In conclusion, MVs from human MSCs inhibited in vitro cell growth and survival of different tumor cell lines and in vivo progression of established tumors.
间充质干细胞(MSCs)对肿瘤生长具有相反的影响,既能促进血管生成和肿瘤起始,又能抑制已建立的肿瘤的进展。肿瘤微环境中 MSC 产生的因子可能与其生物学效应有关。最近的研究表明,微泡(MVs)是肿瘤微环境中细胞间通讯的一个组成部分。在本研究中,我们评估了源自人骨髓间充质干细胞的 MVs 是否可能刺激或抑制 HepG2 肝癌、卡波济肉瘤和 Skov-3 卵巢肿瘤细胞系的体外和体内生长。我们发现 MVs 抑制了所有细胞系的细胞周期进程,并诱导了 HepG2 和卡波济细胞的细胞凋亡和 Skov-3 细胞的坏死。观察到的细胞周期负调控因子的激活可能解释了这些生物学效应。在荷瘤小鼠中,通过皮下注射这些细胞系建立的肿瘤内给予 MVs,显著抑制了肿瘤的生长。总之,人 MSCs 的 MVs 抑制了不同肿瘤细胞系的体外细胞生长和存活以及已建立的肿瘤的体内进展。
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