TNFα and TGFβ-1 synergistically increase the cancer stem cell properties of MiaPaCa-2 cells.
TNFα and TGFβ-1 synergistically increase the cancer stem cell properties of MiaPaCa-2 cells.
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DOI：
10.3892/ol.2017.6810
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发表时间：
2017-10
期刊：
影响因子：
2.9
通讯作者：
Belyaev NN
中科院分区：
文献类型：
--
作者：
Kali A;Ostapchuk YO;Belyaev NN
已有研究表明，胰腺癌患者血清肿瘤坏死因子α和转化生长因子α-1水平升高，转化生长因子β-1和转化生长因子β-1水平升高。此外，外源性暴露于这些细胞因子可促进多种癌细胞侵袭和肿瘤干细胞(CSC)表型。然而，它们在胰腺CSCs中的重要性仍然难以捉摸。本研究检测了肿瘤坏死因子α和转化生长因子β-1对人PC细胞系MIaPaCa-2的影响。流式细胞仪检测结果显示，在贴壁肿瘤细胞培养条件下，肿瘤坏死因子α和转化生长因子β-1协同增加分化簇(CD44v6)、CD133和三磷酸腺苷结合盒转运体G2(ABCG2)的表达。此外，在球状培养条件下用这些细胞因子预处理的细胞中也观察到了类似的趋势。与以往的研究相似，肿瘤坏死因子α处理增加了贴壁培养中表达表皮生长因子受体的细胞的比例，这一结果得到了球体形成实验的进一步支持，在球体形成实验中，高比例表达表皮生长因子受体的细胞的传代培养显示出最有效的球体形成能力。然而，单独或联合使用这些细胞因子时，表达血管内皮生长因子受体1(VEGFR1)的细胞比例并没有增加。这一数据随后得到了伤口愈合试验的结果的支持，在该试验中，细胞因子治疗不会增加细胞的迁移。四甲基偶氮唑盐比色法和细胞毒试验结果显示，肿瘤坏死因子α和转化生长因子β-1联合作用可显著增加细胞的增殖和柔红霉素耐药性，但对吉西他滨的耐药性无明显影响。综上所述，本研究数据提供了肿瘤坏死因子α、转化生长因子β-1与MiaPaCa-2细胞的肿瘤干细胞特性之间的机制联系。提示靶向肿瘤坏死因子α和转化生长因子β-1的治疗有利于提高PC患者的治疗效果。
Increased serum concentrations of tumor necrosis factor α (TNFα) and transforming growth factor β-1 (TGFβ-1) in the blood of patients with pancreatic cancer (PC) have previously been demonstrated. In addition, exogenous exposure to these cytokines promotes various cancer cell invasive and cancer stem cell (CSC) phenotypes. However, their importance in pancreatic CSCs remains elusive. In the present study, the effects of TNFα and TGFβ-1 on the human PC cell line MiaPaCa-2 were examined. Using flow cytometry, it was revealed that TNFα and TGFβ-1 synergistically increase cluster of differentiation (CD) 44v6, CD133 and ATP-binding cassette transporter G2 (ABCG2) expressing populations in adherent tumor cell culture conditions. Furthermore, a similar trend was observed in cells pretreated with these cytokines grown in sphere forming culture conditions. Similar to previous studies, TNFα treatment increased the proportion of epidermal growth factor receptor (EGFR) expressing cells in adherent culture, and this data was further supported by the results of the sphere formation assay, in which the subculture with a high proportion of EGFR expressing cells exhibited the most efficient sphere forming ability. However, the proportion of vascular endothelial growth factor receptor 1 (VEGFR1) expressing cells did not increase upon treatment with these cytokines individually or in combination. This data was subsequently supported by the results of the wound healing assay in which cytokine treatment did not increase the migration of cells. The MTT cell proliferation and cytotoxicity assay revealed that TNFα + TGFβ-1 treatment significantly increased cell proliferation and daunorubicin resistance, but not gemcitabine resistance. In conclusion, the data of the current study provide a mechanistic association between TNFα, TGFβ-1 and the CSC properties of MiaPaCa-2 cells. In addition, it suggests that targeting TNFα and TGFβ-1 is beneficial for improving the therapeutic efficacy of treatments for patients with PC.
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影响因子：
5.2
作者：
Ho, Ming-Yi;Tang, Shye-Jye;Sun, Kuang-Hui
通讯作者：
Sun, Kuang-Hui
影响因子：
2.3
作者：
Poch, Bertram;Lotspeich, Errki;Gansauge, Frank
通讯作者：
Gansauge, Frank
影响因子：
8.4
作者：
Monzani, Elena;Facchetti, Floriana;La Porta, Caterina A. M.
通讯作者：
La Porta, Caterina A. M.
影响因子：
4.8
作者：
Bao, Bin;Azmi, Asfar S.;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
肿瘤复发的细胞来源破译将CD44鉴定为胰腺腺癌的主要治疗靶点。
影响因子：
--
作者：
Molejon MI;Tellechea JI;Loncle C;Gayet O;Gilabert M;Duconseil P;Lopez-Millan MB;Moutardier V;Gasmi M;Garcia S;Turrini O;Ouaissi M;Poizat F;Dusetti N;Iovanna J
通讯作者：
Iovanna J