Cytokines and growth factors stimulate hyaluronan production: role of hyaluronan in epithelial to mesenchymal-like transition in non-small cell lung cancer.
Cytokines and growth factors stimulate hyaluronan production: role of hyaluronan in epithelial to mesenchymal-like transition in non-small cell lung cancer.
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DOI：
10.1155/2010/485468
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发表时间：
2010
影响因子：
--
通讯作者：
Mulshine JL
中科院分区：
文献类型：
--
作者：
Chow G;Tauler J;Mulshine JL
在这项研究中，我们研究了透明质酸（HA）在非小细胞肺癌（NSCLC）中的作用，因为HA水平与恶性程度密切相关。HA是一种丰富的细胞外基质成分，其合成受生长因子和细胞因子（包括表皮生长因子（EGF）和白细胞介素-1 β（IL-1β））调节。我们表明，单独使用重组EGF和IL-1β或与TGF-β联合使用能够刺激肺腺癌细胞系A549中HA的产生。TGF-β/IL-1β处理诱导上皮细胞向间充质样表型转变（EMT），改变细胞形态和波形蛋白和E-钙粘蛋白的表达。我们还在上皮性肺腺癌细胞系H358中过表达透明质酸合成酶-3（HAS 3），导致诱导HA表达，EMT表型，增强MMP 9和MMP 2活性和增加侵袭。此外，向A549细胞中加入外源性HA并诱导HA H358细胞导致对表皮生长因子受体（EGFR）抑制剂易瑞沙的抗性增加。 总之，这些结果表明，HA产生的增加能够诱导EMT并增加NSCLC对易瑞沙的耐药性。因此，调控HA水平可能成为NSCLC治疗干预的新靶点。
In this study, we investigated the role of hyaluronan (HA) in non-small cell lung cancer (NSCLC) since close association between HA level and malignancy has been reported. HA is an abundant extracellular matrix component and its synthesis is regulated by growth factors and cytokines that include epidermal growth factor (EGF) and interleukin-1β (IL-1β). We showed that treatment with recombinant EGF and IL-1β, alone or in combination with TGF-β, was able to stimulate HA production in lung adenocarcinoma cell line A549. TGF-β/IL-1β treatment induced epithelial to mesenchymal-like phenotype transition (EMT), changing cell morphology and expression of vimentin and E-cadherin. We also overexpressed hyaluronan synthase-3 (HAS3) in epithelial lung adenocarcinoma cell line H358, resulting in induced HA expression, EMT phenotype, enhanced MMP9 and MMP2 activities and increased invasion. Furthermore, adding exogenous HA to A549 cells and inducing HA H358 cells resulted in increased resistance to epidermal growth factor receptor (EGFR) inhibitor, Iressa. Together, these results suggest that elevated HA production is able to induce EMT and increase resistance to Iressa in NSCLC. Therefore, regulation of HA level in NSCLC may be a new target for therapeutic intervention.
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影响因子：
4.8
作者：
Bourguignon, Lilly Y. W.;Gilad, Eli;Peyrollier, Karine
通讯作者：
Peyrollier, Karine
影响因子：
7.5
作者：
Deeb, G;Wang, JM;Tan, DF
通讯作者：
Tan, DF
影响因子：
5.7
作者：
Fukuyama, Takashi;Ichiki, Yoshinobu;Yasumoto, Kosei
通讯作者：
Yasumoto, Kosei
影响因子：
254.7
作者：
Greenlee, RT;Murray, T;Wingo, PA
通讯作者：
Wingo, PA
DOI：
10.1083/jcb.120.3.825
发表时间：
1993-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Knudson CB
通讯作者：
Knudson CB