Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer.
Shed Syndecan-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer.
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Shed Syndecan-1 通过 EGFR 通路参与结直肠癌化疗耐药
DOI：
10.1038/bjc.2014.493
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发表时间：
2014-11-11
影响因子：
8.8
通讯作者：
Ba, Y.
中科院分区：
文献类型：
--
作者：
Wang, X.;Zuo, D.;Chen, Y.;Li, W.;Liu, R.;He, Y.;Ren, L.;Zhou, L.;Deng, T.;Wang, X.;Ying, G.;Ba, Y.
背景：基质金属蛋白酶-7（MMP-7）和其他蛋白酶诱导的多配体蛋白聚糖-1（Sdc-1）脱落在癌症发展中具有重要作用。方法：采用酶联免疫吸附试验（ELISA）、斑点杂交（Dot blot）、逆转录-PCR（RT-PCR）、免疫组化等方法检测Sdc-1在大肠癌中的脱落情况，采用胶原凝胶滴包埋培养-药敏试验（CD-DST）和MTT法检测Sdc-1对化疗药物敏感性的影响（3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑），并通过斑点印迹，蛋白质印迹和免疫荧光的潜在作用机制。结直肠癌患者Sdc-1脱落增加，术后患者血清Sdc-1水平低于术前患者，但仍高于在健康成人中观察到的那些。术前血清Sdc-1水平高的患者对5-氟尿嘧啶、奥沙利铂、伊立替康、顺铂或紫杉醇化疗的反应较低。此外，术前Sdc-1血清水平高的患者的无病生存率明显较差。结直肠癌化疗耐药的机制可能与Sdc-1脱落有关，Sdc-1的脱落可增强EGFR的磷酸化和下游信号转导。结论：Sdc-1通过EGFR途径参与结直肠癌化疗耐药的发生，血清Sdc-1水平可能成为结直肠癌新的预后指标。
Background:Syndecan-1 (Sdc-1) shedding induced by matrix metalloproteinase-7 (MMP-7) and additional proteases has an important role in cancer development. However, the impact of Sdc-1 shedding on chemotherapeutic resistance has not been reported.Methods:We examined Sdc-1 shedding in colorectal cancer by enzyme-linked immunosorbent assay (ELISA), Dot blot, reverse transcription-PCR (RT-PCR), immunohistochemistry and so on, its impact on chemotherapeutic sensitivity by collagen gel droplet embedded culture-drug sensitivity test (CD-DST) and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide), and potential mechanisms of action by Dot blot, western blot and immunofluorescence.Results:Sdc-1 shedding was increased in colorectal cancer patients, Sdc-1 serum levels in postoperative patients were lower than in preoperative patients, but still higher than those observed in healthy adults. Patients with high preoperative Sdc-1 serum levels were less responsive to 5-Fluorouracil, Oxaliplatin, Irintecan, Cisplatin or Paclitaxel chemotherapy. Moreover, the disease-free survival of patients with high preoperative Sdc-1 serum levels was significantly poorer. The possible mechanism of chemotherapy resistance in colorectal cancer can be attributed to Sdc-1 shedding, which enhances EGFR phosphorylation and downstream signalling.Conclusions:Shed Sdc-1 is involved in chemotherapy resistance via the EGFR pathway in colorectal cancer, and Sdc-1 serum levels could be a new prognostic marker in colorectal cancer.
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影响因子：
1.6
作者：
Kim, Mihye;Murakami, Akira;Ohigashi, Hajime
通讯作者：
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作者：
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通讯作者：
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