Detection of a soluble form of CD109 in serum of CD109 transgenic and tumor xenografted mice.

Detection of a soluble form of CD109 in serum of CD109 transgenic and tumor xenografted mice.
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DOI:
10.1371/journal.pone.0083385
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Takahashi M
Takahashi M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sakakura H;Murakumo Y;Mii S;Hagiwara S;Kato T;Asai M;Hoshino A;Yamamoto N;Sobue S;Ichihara M;Ueda M;Takahashi M

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CD 109是一种糖基磷脂酰肌醇锚定的糖蛋白,在包括鳞状细胞癌在内的一些人类肿瘤中以高水平表达。据报道,由于CD 109被弗林蛋白酶切割,其可溶形式在体外分泌到培养基中,我们假设CD 109可以作为体内肿瘤标志物。在这项研究中,我们使用过表达小鼠CD 109的转基因小鼠(mCD 109-TG小鼠)和接种过表达人CD 109(hCD 109)的HEK 293细胞的肿瘤异种移植小鼠研究了CD 109作为一种新的血清肿瘤标志物。在mCD 109-TG小鼠的血清和尿液中,使用蛋白质印迹法检测mCD 109。在异种移植小鼠中,使用蛋白质印迹和CD 109 ELISA在血清中检测到从接种的肿瘤分泌的hCD 109。肿瘤分泌的CD 109的浓度随着肿瘤增大而成比例地增加。分泌的CD 109的浓度显着下降,肿瘤切除后17小时,并成为切除后48小时检测不到。肿瘤分泌的CD 109的半衰期约为5.86±0.17 h。这些结果表明,CD 109是存在于血清中作为一种可溶性形式,并建议其作为一种新的肿瘤标记物在癌症患者表达CD 109的潜力。
CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is expressed at high levels in some human tumors including squamous cell carcinomas. As CD109 is reportedly cleaved by furin and its soluble form is secreted into culture medium in vitro, we hypothesized that CD109 could serve as a tumor marker in vivo. In this study, we investigated CD109 as a novel serum tumor marker using transgenic mice that overexpress mouse CD109 (mCD109-TG mice) and tumor xenografted mice inoculated with human CD109 (hCD109)-overexpressing HEK293 cells. In sera and urine of mCD109-TG mice, mCD109 was detected using western blotting. In xenografted mice, hCD109 secreted from inoculated tumors was detected in sera, using western blotting and CD109 ELISA. Concentrations of tumor-secreted CD109 increased proportionally as tumors enlarged. Concentrations of secreted CD109 decreased notably by 17 h after tumor resection, and became undetectable 48 h after resection. The half-life of tumor-secreted CD109 was about 5.86±0.17 h. These results indicate that CD109 is present in serum as a soluble form, and suggest its potential as a novel tumor marker in patients with cancers that express CD109.
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