TSHR调控人甲状腺癌细胞增殖和转移能力的机制及其潜在临床意义

The clinical endocrine therapy based on inhibition of TSH synthesis has been used for many years, however it's effect on prevention the recurrence of differentiated thyroid carcinoma (DTC) is still not clear. We recently discovered that the expression of TSH receptor (TSHR) had not been significantly upregulated in differentiated thyroid cancer, and down-regulation of TSHR only mildly inhibited thyroid cancer cell proliferation, but significantly enhanced the metastatic ability. These results suggested the lack of theoretical basis in endocrine therapy. Aiming to further evaluate the role of TSH and TSHR in the inhibition of recurrence and metastasis in DTC, this study was designed to verify the effect and mechanism of TSHR signal transduction pathway in regulating the metastasis and proliferation ability for differentiated thyroid cancer cells and stem cell-like cancer cell; explore the interaction of TSHR and integrinα(V)β(3) in DTC cell proliferation and metastases, and detect the role and mechanism of such genes in DTC metastases using the EMT model; screen molecular targets guiding individual endocrine therapy. The expected results will provide theoretical basis for correction of endocrine treatment options in differentiated thyroid cancer.

尽管以抑制TSH为主的内分泌治疗已在临床应用多年，但其预防分化型甲状腺癌（DTC）复发的效果目前尚不明确。我们新近发现：在分化型甲状腺癌中，TSH受体（TSHR）的表达并无明显上调，而下调TSHR仅轻度抑制甲状腺癌细胞的增殖但显著增强其转移能力。提示：该内分泌治疗缺乏理论基础。为进一步探讨TSH和TSHR在抑制DTC复发和转移中的作用，本课题拟通过分子细胞生物学实验、体内实验和临床研究等方法，探讨抑制TSHR信号转导通路对分化型甲状腺癌细胞及干细胞样癌细胞的转移和增殖能力的调控作用，阐明其分子机制，同时研究TSHR和integrinα(V)β(3)等基因在DTC细胞转移和增殖中的相互作用，结合EMT为模型研究其在DTC转移过程中的作用机制，并筛选指导个体化内分泌治疗的分子指标。所得的结果将为修正分化型甲状腺癌的内分泌治疗方案提供理论基础。

尽管以抑制 TSH 为主的内分泌治疗已在临床应用多年，但其预防分化型甲状腺癌（DTC）复发的效果目前尚不明确。我们新近发现：在分化型甲状腺癌中，TSH 受体（TSHR）的表达并无明显上调，而下调 TSHR 仅轻度抑制甲状腺癌细胞的增殖但显著增强其转移能力。提示：该内分泌治疗缺乏理论基础。为进一步探讨 TSH 和TSHR 在抑制 DTC 复发和转移中的作用，本课题拟通过分子细胞生物学实验、体内实验和临床研究等方法，探讨抑制 TSHR 信号转导通路对分化型甲状腺癌细胞及干细胞样癌细胞的转移和增殖能力的调控作用， 阐明其分子机制，同时研究 TSHR 和 integrinα(V)β(3)等基因在 DTC 细胞转移和增殖中的相互作用，结合 EMT 为模型研究其在 DTC 转移过程中的作用机制， 并筛选指导个体化内分泌治疗的分子指标。所得的结果将为修正分化型甲状腺癌的内分泌治疗方案提供理论基础。