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Clinical and Developmental Immunology
Volume 2013, Article ID 712561, 11 pages
Research Article

Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7

1Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine (SJTUSM), 225 South Chongqing Road, Shanghai 200025, China
2Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated First People’s Hospital, 100 Haining Road, Shanghai 200080, China
3Department of Endocrinology and Metabolism, Ruijin Hospital, SJTUSM, 197 Ruijin 2nd Road, Shanghai 200025, China
4Shanghai Institute of Immunology, Institutes of Medical Sciences, SJTUSM, 280 South Chongqing Road, Shanghai 200025, China
5Department of Endocrinology and Metabolism, The First Affiliated Hospital of Bengbu Medical College and Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Bengbu 233004, China
6Cancer Hospital, HeFei Institutes of Physical Science, Chinese Academy of Science, 350 Shushan Lake Road, HeFei 230031, China

Received 9 August 2013; Accepted 12 October 2013

Academic Editor: Marco Antonio Velasco-Velázquez

Copyright © 2013 Shipeng Dang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 ( ) and tumor growth ( ). 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.