Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7.
Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7.
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DOI：
10.1155/2013/712561
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发表时间：
2013
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Dang S;Peng Y;Ye L;Wang Y;Qian Z;Chen Y;Wang X;Lin Y;Zhang X;Sun X;Wu Q;Cheng Y;Nie H;Jin M;Xu H
在炎症部位，高分子量透明质酸片段降解为低分子量透明质酸片段（LMW-HA）以调节免疫应答。然而，LMW-HA在PTC进展中的功能仍有待阐明。在本研究中，我们发现LMW-HA的受体TLR 4在PTC组织和细胞系W3中异常过表达。W3细胞暴露于LMW-HA通过TLR 4促进细胞增殖和迁移。TLR 4的敲低提供了TLR 4对于LMW-HA诱导的CXCR 7表达是必需的证据，CXCR 7负责LMW-HA诱导的W3细胞的增殖和迁移。在荷瘤成年裸鼠中，LMW-HA对W3细胞的刺激促进肿瘤块中CXCR 7的表达（P = 0.002）和肿瘤生长（P < 0.001）。为了进一步证实我们的研究结果，我们研究了TLR 4和CXCR 7表达的临床病理意义，使用免疫组化在135人PTC组织和56例正常甲状腺组织样本。PTC组织中TLR 4和CXCR 7的阳性表达率分别为53%和24%。TLR 4和CXCR 7的表达与肿瘤大小和淋巴结转移有关。因此，LMW-HA可能通过TLR 4/CXCR 7通路参与PTC的发生发展，可能成为PTC免疫调节治疗的新靶点。
In inflammatory sites, high molecular weight hyaluronan fragments are degraded into lower molecular weight hyaluronan fragments (LMW-HA) to regulate immune responses. However, the function of LMW-HA in PTC progression remains to be elucidated. In this study, we found that receptor of LMW-HA, TLR4, was aberrantly overexpressed in PTC tissues and cell line W3. Exposure of W3 cells to LMW-HA promoted cell proliferation and migration via TLR4. Knockdown of TLR4 has provided evidence that TLR4 is essential for LMW-HA-induced CXCR7 expression, which is responsible for LMW-HA-induced proliferation and migration of W3 cells. In tumor-bearing adult nude mice, stimulation of LMW-HA on W3 cells promotes CXCR7 expression in tumor masses (P = 0.002) and tumor growth (P < 0.001). To further confirm our findings, we investigated the clinicopathologic significance of TLR4 and CXCR7 expression using immumohistochemistry in 135 human PTC tissues and 56 normal thyroid tissue samples. Higher rates of TLR4 (53%) and CXCR7 (24%) expression were found in PTC tissues than in normal tissues. Expression of TLR4 or CXCR7 is associated with tumor size and lymph node metastasis. Therefore, LMW-HA may contribute to the development of PTC via TLR4/CXCR7 pathway, which may be a novel target for PTC immunomodulatory therapy.
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影响因子：
--
作者：
Nikitovic D;Kouvidi K;Karamanos NK;Tzanakakis GN
通讯作者：
Tzanakakis GN
影响因子：
4
作者：
Dusio, Giuseppina F.;Cardani, Diego;Rumio, Cristiano
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Rumio, Cristiano
影响因子：
5.4
作者：
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Chen, Lidian
影响因子：
6.5
作者：
SATTAR, A;ROONEY, P;LEDGER, P
通讯作者：
LEDGER, P
影响因子：
8
作者：
Luker, K. E.;Lewin, S. A.;Mihalko, L. A.;Schmidt, B. T.;Winkler, J. S.;Coggins, N. L.;Thomas, D. G.;Luker, G. D.
通讯作者：
Luker, G. D.