Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7
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, w...
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2013-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2013/712561 |
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| author | Shipeng Dang Yongde Peng Lei Ye Yanan Wang Zhongqing Qian Yuqing Chen Xiaojing Wang Yunzhi Lin Xiaomei Zhang Xiyan Sun Qiong Wu Yiji Cheng Hong Nie Min Jin Huanbai Xu |
| author_facet | Shipeng Dang Yongde Peng Lei Ye Yanan Wang Zhongqing Qian Yuqing Chen Xiaojing Wang Yunzhi Lin Xiaomei Zhang Xiyan Sun Qiong Wu Yiji Cheng Hong Nie Min Jin Huanbai Xu |
| author_sort | Shipeng Dang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dce1028addd049fc9e34bd111872c868 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-dce1028addd049fc9e34bd111872c8682025-02-03T01:07:21ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/712561712561Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7Shipeng Dang0Yongde Peng1Lei Ye2Yanan Wang3Zhongqing Qian4Yuqing Chen5Xiaojing Wang6Yunzhi Lin7Xiaomei Zhang8Xiyan Sun9Qiong Wu10Yiji Cheng11Hong Nie12Min Jin13Huanbai Xu14Institute 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, ChinaDepartment of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated First People’s Hospital, 100 Haining Road, Shanghai 200080, ChinaDepartment of Endocrinology and Metabolism, Ruijin Hospital, SJTUSM, 197 Ruijin 2nd Road, Shanghai 200025, ChinaShanghai Institute of Immunology, Institutes of Medical Sciences, SJTUSM, 280 South Chongqing Road, Shanghai 200025, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaCancer Hospital, HeFei Institutes of Physical Science, Chinese Academy of Science, 350 Shushan Lake Road, HeFei 230031, ChinaInstitute 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, ChinaInstitute 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, ChinaShanghai Institute of Immunology, Institutes of Medical Sciences, SJTUSM, 280 South Chongqing Road, Shanghai 200025, ChinaInstitute 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, ChinaDepartment of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated First People’s Hospital, 100 Haining Road, Shanghai 200080, ChinaIn 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.http://dx.doi.org/10.1155/2013/712561 |
| spellingShingle | Shipeng Dang Yongde Peng Lei Ye Yanan Wang Zhongqing Qian Yuqing Chen Xiaojing Wang Yunzhi Lin Xiaomei Zhang Xiyan Sun Qiong Wu Yiji Cheng Hong Nie Min Jin Huanbai Xu Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7 Clinical and Developmental Immunology |
| title | Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7 |
| title_full | Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7 |
| title_fullStr | Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7 |
| title_full_unstemmed | Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7 |
| title_short | Stimulation of TLR4 by LMW-HA Induces Metastasis in Human Papillary Thyroid Carcinoma through CXCR7 |
| title_sort | stimulation of tlr4 by lmw ha induces metastasis in human papillary thyroid carcinoma through cxcr7 |
| url | http://dx.doi.org/10.1155/2013/712561 |
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