Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines.
Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines.
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DOI：
10.1186/s13287-016-0282-7
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发表时间：
2016-02-09
影响因子：
7.5
通讯作者：
Schmid RA
中科院分区：
文献类型：
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作者：
Cortes-Dericks L;Froment L;Kocher G;Schmid RA
间充质干细胞分泌的可溶性因子被认为支持或抑制肿瘤生长。在此，我们研究了人肺源性间充质干细胞条件培养基（hlMSC-CM）是否在恶性胸膜间皮瘤细胞系H28、H2052和Meso 4中发挥抗肿瘤活性。从人肺源性间充质干细胞收集hlMSC-CM。肿瘤细胞生长的抑制基于分别使用XTT和BrdU测定的细胞活力的降低和细胞增殖的抑制。通过锚定非依赖性球体形成测定评估肿瘤球体的消除。通过基于荧光的细胞因子阵列测定hlMSC-CM的细胞因子谱。我们的数据显示hlMSC-CM含有广泛的可溶性因子，包括：细胞因子、趋化因子、激素、生长和血管生成因子、基质金属蛋白酶、金属蛋白酶抑制剂和细胞-细胞介导蛋白。H28、H2052和Meso 4细胞系的48小时和72小时hlMSC-CM处理引起细胞活力的显著降低并抑制细胞增殖。H28细胞的72小时hlMSC-CM孵育完全消除了耐药球形成细胞，这比顺铂的半数最大抑制浓度的两倍更有效。我们的研究结果表明，无细胞hlMSC-CM赋予体外抗肿瘤活性，通过可溶性因子在测试的间皮瘤细胞，因此，可以作为一种治疗工具，以增加目前的治疗策略，在恶性胸膜间皮瘤。本文的在线版本（doi：10.1186/s13287-016-0282-7）包含补充材料，可供授权用户使用。
The soluble factors secreted by mesenchymal stem cells are thought to either support or inhibit tumor growth. Herein, we investigated whether the human lung-derived mesenchymal stem cell-conditioned medium (hlMSC-CM) exerts antitumor activity in malignant pleural mesothelioma cell lines H28, H2052 and Meso4. hlMSC-CM was collected from the human lung-derived mesenchymal stem cells. Inhibition of tumor cell growth was based on the reduction of cell viability and inhibition of cell proliferation using the XTT and BrdU assays, respectively. Elimination of tumor spheroids was assessed by the anchorage-independent sphere formation assay. The cytokine profile of hlMSC-CM was determined by a chemiluminescence-based cytokine array. Our data showed that hlMSC-CM contains a broad range of soluble factors which include: cytokines, chemokines, hormones, growth and angiogenic factors, matrix metalloproteinases, metalloproteinase inhibitors and cell–cell mediator proteins. The 48- and 72-hour hlMSC-CM treatments of H28, H2052 and Meso4 cell lines elicited significant decreases in cell viability and inhibited cell proliferation. The 72-hour hlMSC-CM incubation of H28 cells completely eliminated the drug-resistant sphere-forming cells, which is more potent than twice the half maximal inhibitory concentration of cisplatin. Our findings indicate that the cell-free hlMSC-CM confers in vitro antitumor activities via soluble factors in the tested mesothelioma cells and, hence, may serve as a therapeutic tool to augment the current treatment strategies in malignant pleural mesothelioma. The online version of this article (doi:10.1186/s13287-016-0282-7) contains supplementary material, which is available to authorized users.