Inhibitory effects of retinoic acid on invasiveness of human thyroid carcinoma cell lines in vitro

被引:1
作者
Lan, L. [1 ]
Cui, D. [2 ]
Luo, Y. [3 ]
Shi, B. Y. [4 ]
Deng, L. L. [1 ]
Zhang, G. Y. [1 ]
Wang, H. [1 ]
机构
[1] Peking Univ, Med Coll 4, Beijing Ji Shui Tan Hosp, Dept Endocrinol, Beijing 100035, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Endocrinol, Nanjing, Peoples R China
[3] Capital Med Univ, Beijing Anzhen Hosp, Dept Urol, Beijing, Peoples R China
[4] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Endocrinol, Coll Med, Xian 710049, Peoples R China
基金
中国国家自然科学基金;
关键词
C643; HTH74; invasion; retinoic acid; thyroid carcinoma; REDIFFERENTIATION THERAPY; TUMOR INVASION; EXTRACELLULAR-MATRIX; UROKINASE RECEPTOR; GROWTH-FACTOR; CANCER; EXPRESSION; OVEREXPRESSION; METASTASES; MIGRATION;
D O I
10.1007/BF03346528
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The prognosis of patients with metastasized thyroid carcinoma is not optimistic, necessitating the search for new treatment options. Aim: Beneficial effects of retinoic acid (RA) have been suggested in thyroid cancer differentiation and the present study was per-Formed to investigate the anti-metastatic potential of RA in respect of important determinants of metastatic behavior in thyroid carcinoma, focusing on the role of invasion-associated proteins. Materials and methods: Differentiated thyroid carcinoma cell lines FTC-133 and XTC.UC1, and anaplastic thyroid cancer cell lines C643 and HTH74 were studied. All cell lines were cultured with all-trans-RA (ATRA) or the solvent ethanol. Invasion and adhesion potency in vitro was studied by transwell experiment and short-term adhesion assay. The involvement of invasion-associated proteins, urokinase type plasminogen activator (uPA), uPA receptor (uPAR), matrixmetalloproteinase-2 (MMP-2) and E-cadherin, were investigated by semi-quantitative RT-PCR and Western blot. Results: In vitro invasion assay revealed that ATRA treatment could reduce the invasive potency in all the thyroid cancer cell lines, with the most significant effect in anaplastic cancer cells. Short-term adhesion assay suggested that ATRA increases cancer cell adhesion to extracellular matrix (ECM) in C643, HTH74 and XTC.UC1, probably through a transcriptional and translational regulation of some attachment molecules. RT-PCR and Western blot both revealed diminished expression of uPAR in all four carcinoma cell lines. In C643 and HTH74 cell lines, the expression of uPA was reduced and the expression of E-cadherin was increased, whereas the MMP-2 expression was not significantly down-regulated in ATRA-treated group. In ATRA-treated FTC-133 and XTC.UC1 cell lines, MMP-2 expression was decreased, but no significant changes in uPA and E-cadherin expression were observed. Conclusions: The present study demonstrates the influence of ATRA on both important determinants of metastatic behavior ("de-adhesion" and proteolysis) in thyroid carcinoma cell lines, especially in anaplastic cancer cells. These findings may add to the explanations for beneficial effects of RA in the treatment of metastatic thyroid carcinomas. (J. Endocrinol. Invest. 32: 731-738, 2009) (C) 2009, Editrice Kurtis
引用
收藏
页码:731 / 738
页数:8
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