Differential pattern of integrin receptor expression in differentiated and anaplastic thyroid cancer cell lines
Differential pattern of integrin receptor expression in differentiated and anaplastic thyroid cancer cell lines
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DOI：
10.1089/thy.2005.15.1011
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发表时间：
2005-09-01
期刊：
影响因子：
6.6
通讯作者：
Zielke, A
中科院分区：
文献类型：
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作者：
Hoffmann, S;Maschuw, K;Zielke, A
肿瘤细胞与细胞外基质（ECM）的粘附是转移性疾病发展的关键步骤，并且由特异性整合素受体分子（Integrin receptor molecules，ECM）介导。甲状腺癌（TC）的不同组织类型之间转移扩散的模式有很大不同.然而，到目前为止，只有偶尔在TC中表征了T-SMA。在10个分化的TC细胞系（FTC 133、236、238、HTC、HTC TSHr、XTC、PTC 4.0/4.2、TPC 1、Kat 5）和两个间变性TC细胞系（ATC、C643、Hth 74）、正常甲状腺组织（Thy 1、3）和甲状腺癌标本（TCS）的原代培养物中研究了Tcl 3的表达。通过荧光激活细胞分选仪（FACS）和免疫组织化学染色分析16种β 1-4、β 7、α-6、α V、α IIb、α L、α M、α X）和4种β异源二聚体（α 2 β 1、α 5 β 1、α V β 3、α V β 5）的表达。评估甲状腺肿瘤细胞对ECM蛋白的粘附及其对促甲状腺激素（TSH）的应答的表达。滤泡TC细胞系呈现高水平的整合素α 2、α 3、α 5、β 1、β 3和低水平的α 1，而乳头状细胞系表达以α 5和β 1为主的异质性模式的整合素。ATC主要显示整合素α 2、α 3、α 5、α 6、β 1和低水平的α 1、α 4和α V。整合素异二聚体与单体表达相关。对TCS的评估在很大程度上证实了这些结果，但很少有例外，即alpha 4、alpha 6和beta 3。TC细胞系粘附于纯化ECM蛋白的能力与CD 34表达相关。TSH诱导TC细胞粘附在剂量依赖性的方式，尽管一个不变的数组的表达或特定的api的水平。不同组织发生学背景的甲状腺癌细胞系显示出与肿瘤侵袭性相关的截然不同的表达模式。与ECM蛋白的体外粘附和ECM表达一致。最后，促甲状腺激素刺激的甲状腺肿瘤细胞系与ECM的粘附可能与β-淀粉样蛋白表达的改变无关。
Adhesion of tumor cells to the extracellular matrix (ECM) is a crucial step for the development of metastatic disease and is mediated by specific integrin receptor molecules (IRM). The pattern of metastatic spread differs substantially amoung the various histotypes of thyroid cancer (TC). However, IRM have only occasionally been characterized in TC until now. IRM expression was investigated in 10 differentiated (FTC133, 236, 238, HTC, HTC TSHr, XTC, PTC4.0/4.2, TPC1, Kat5) and two anaplastic TC cell lines (ATC, C643, Hth74), primary cultures of normal thyroid tissue (Thy1,3), and thyroid cancer specimens (TCS). Expression of 16 IRM beta 1-4, beta 7, alpha-6, alpha V, alpha IIb, alpha L, alpha M, alpha X) and of four IRM heterodimers (alpha 2 beta 1, alpha 5 beta 1, alpha V beta 3, alpha V beta 5), was analyzed by fluorescent-activated cell sorter (FACS) and immunohistochemical staining. Thyroid tumor cell adhesion to ECM proteins and their IRM expression in response to thyrotropin (TSH) was assessed. Follicular TC cell lines presented high levels of integrins alpha 2, alpha 3, alpha 5, beta 1, beta 3 and low levels of alpha 1, whereas papillary lines expressed a heterogenous pattern of IRM, dominated by alpha 5 and beta 1. ATC mainly displayed integrins alpha 2, alpha 3, alpha 5, alpha 6, beta 1 and low levels of alpha 1, alpha 4 and alpha V. Integrin heterodimers correlated with monomer expression. Evaluation of TCS largely confirmed these results with few exeptions, namely alpha 4, alpha 6, and beta 3. The ability of TC cell lines to adhere to purified ECM proteins correlated with IRM expression. TSH induced TC cell adhesion in a dose-dependent fashion, despite an unchanged array of IRM expression or level of a particular IRM. Thyroid carcinoma cell lines of different histogenetic background display profoundly different patterns of IRM expression that appear to correlate with tumor aggressiveness. M vitro adhesion to ECM proteins and IRM expression concur. Finally, TSH-stimulated adhesion of thyroid tumor cell lines to ECM may not be associated with altered IRM expression.