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17β-雌二醇抑制 IL-8-Src 信号轴抑制人骨髓间充质干细胞介导的胃癌侵袭。

Suppression of IL-8-Src signalling axis by 17β-estradiol inhibits human mesenchymal stem cells-mediated gastric cancer invasion.

机构信息

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

J Cell Mol Med. 2016 May;20(5):962-72. doi: 10.1111/jcmm.12786. Epub 2016 Mar 6.

DOI:10.1111/jcmm.12786
PMID:26945908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4831355/
Abstract

Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17β -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17β-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17β-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells.

摘要

流行病学数据显示，全球男性胃癌发病率是女性的两倍。有报道称，雌激素具有抑制胃癌发展的作用。内源性雌激素降低了女性的胃癌发病率。接受雌激素治疗的癌症患者随后患胃癌的风险较低。越来越多的研究报告称，骨髓间充质干细胞（BMMSCs）可能通过旁分泌可溶性因子促进胃癌的进展。在这里，我们进一步探讨了雌激素对 BMMSCs 介导的人类胃癌侵袭性运动的影响。我们发现 HBMMSCs 明显分泌白细胞介素-8（IL-8）蛋白。施用 IL-8 特异性中和抗体可显著抑制 HBMMSCs 介导的胃癌运动。重组 IL-8 可溶性蛋白的处理证实了 IL-8 在介导 HBMMSCs 上调细胞运动中的作用。IL-8 通过Src 信号通路在上皮性胃癌中上调运动活性。我们进一步观察到 17β-雌二醇通过抑制人胃癌细胞中 IL8-Src 信号的激活来抑制 HBMMSCS 诱导的细胞运动。17β-雌二醇抑制 IL8 上调的 Src 下游靶蛋白，包括 p-Cas、p-paxillin、p-ERK1/2、p-JNK1/2、MMP9、tPA 和 uPA。这些结果表明，17β-雌二醇通过抑制人胃癌细胞中 IL8-Src 信号轴，显著抑制 HBMMSCS 诱导的侵袭性运动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/de425625e15f/JCMM-20-962-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/059bbb773f83/JCMM-20-962-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/fcd10d665bb9/JCMM-20-962-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/a609d0502be5/JCMM-20-962-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/4bd3a1489d94/JCMM-20-962-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/ee1a595aca35/JCMM-20-962-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/de425625e15f/JCMM-20-962-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/059bbb773f83/JCMM-20-962-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/fcd10d665bb9/JCMM-20-962-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/a609d0502be5/JCMM-20-962-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/4bd3a1489d94/JCMM-20-962-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/ee1a595aca35/JCMM-20-962-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/531b/4831355/de425625e15f/JCMM-20-962-g006.jpg

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