Li Dapeng, Gu Runxia, Yang Xiaoyong, Hu Chuanxiang, Li Yigong, Gao Ming, Yu Yang
Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer Tianjin, China ; Key Laboratory of Cancer Prevention and Therapy Tianjin, China.
Leukemia Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin, China.
Int J Clin Exp Med. 2014 Dec 15;7(12):5111-7. eCollection 2014.
Papillary thyroid cancer (PTC) is the most rapidly increasing endocrine malignancy worldwide. Although less aggressive than the majority malignancies, PTC exhibits extensive cervical lymph node metastasis in early stage of PTC. However, the underlying molecular mechanism of this early-metastasis remains unknown. Toll like receptors (TLRs) constitute a crucial component of the innate immune response to bacterial and viral pathogens. Emerging evidence suggests that TLRs play important roles in cancer progression, invasion and immune evasion, whereas whether TLRs have any role in PTC remains to be clarified. In this study, we found that TLR3 was present in both PTC specimen and various thyroid cancer cell lines. Further IHC analysis of 63 PTC patients revealed that TLR3 expression was associated with cervical metastasis, but not correlated with patients' TNM staging, extrathyroidal invasion. In addition, TLR3 promoted migration of K1 cells in vitro. Activation of TLR3 increased cancer stem cell marker and migration promoting CD44 expression in vitro, indicating that TLR3 might promote metastasis of PTC via modulating CD44 expression. Taken together, our data revealed that TLR3 is correlated with cervical metastasis of PTC and might be an essential prognostic indicator and target for PTC metastasis.
甲状腺乳头状癌(PTC)是全球范围内增长最为迅速的内分泌恶性肿瘤。尽管其侵袭性低于大多数恶性肿瘤,但PTC在疾病早期就会出现广泛的颈部淋巴结转移。然而,这种早期转移的潜在分子机制仍不清楚。Toll样受体(TLRs)是机体对细菌和病毒病原体固有免疫反应的关键组成部分。新出现的证据表明,TLRs在癌症进展、侵袭和免疫逃逸中发挥重要作用,而TLRs在PTC中是否发挥作用仍有待阐明。在本研究中,我们发现TLR3存在于PTC标本和多种甲状腺癌细胞系中。对63例PTC患者的进一步免疫组化分析显示,TLR3表达与颈部转移相关,但与患者的TNM分期、甲状腺外侵犯无关。此外,TLR3在体外促进K1细胞迁移。TLR3激活增加了体外癌症干细胞标志物和促进迁移的CD44表达,表明TLR3可能通过调节CD44表达促进PTC转移。综上所述,我们的数据表明TLR3与PTC的颈部转移相关,可能是PTC转移的重要预后指标和靶点。