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Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7.

ABSTRACT: 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.

SUBMITTER: Dang S

PROVIDER: S-EPMC3865734 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7.

Dang Shipeng S Peng Yongde Y Ye Lei L Wang Yanan Y Qian Zhongqing Z Chen Yuqing Y Wang Xiaojing X Lin Yunzhi Y Zhang Xiaomei X Sun Xiyan X Wu Qiong Q Cheng Yiji Y Nie Hong H Jin Min M Xu Huanbai H

Clinical & developmental immunology 20131202

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 ess ...[more]

PMID: 24363762

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Project description:BackgroundDistant metastasis (DM) is a rare event and has a negative effect on the prognosis for papillary thyroid carcinoma (PTC). The relationship between cervical lymph node metastasis and DM is complicated and unclear. This study aimed to evaluate the impact of N stage subclassification on different distant metastasis sites based on age stratification, especially for patients with papillary thyroid microcarcinoma.MethodsA total of 28,712 patient with PTC cases between 2010 and 2018 were extracted from the Surveillance, Epidemiology, and End Results database. Multivariable logistic regression analysis was utilized to adjust for confounding variables. Risk stratification, including positive lymph node number and lymph node ratio, was established by receiver operating characteristic curves to help predict DM.ResultsLung was the most common metastatic site regardless of N0, N1a disease, or N1b disease. As the N stage increased, the higher the rate of DM identified. After age stratification, only N1b disease significantly increased the risk of lung metastasis (LM; odds ratio, OR = 20.45, P < 0.001) rather than bone metastasis (BM; OR = 3.46, P > 0.05) in younger patients. However, in older patients, N1b disease significantly increased the risk of both LM (OR = 4.10, P < 0.001) and BM (OR = 2.65, P = 0.007). In patients with papillary thyroid microcarcinoma (PTMC), N1a disease did not increase the risk of DM, LM, and BM compared with N0 disease (P > 0.05). Furthermore, combined N stage with risk stratification has well performance in predicting DM (area under the curve, AUC = 0.761). Similar results were shown in PTC patients with LM (AUC = 0.770) and BM (AUC = 0.729).ConclusionOverall, the incidence of DM significantly increased with the progress of N disease after age stratification. N1a disease did not increase the risk of DM in PTMC patients, regardless of LM or BM. Combined N stage with risk stratification may be beneficial for DM prediction.

Dataset Information

Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7.

Publications

Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7.

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