Lysosomal Acid Hydrolases of the Cathepsin Family Are Novel Targets of INSL3 in Human Thyroid Carcinoma Cells
Lysosomal Acid Hydrolases of the Cathepsin Family Are Novel Targets of INSL3 in Human Thyroid Carcinoma Cells
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DOI：
10.1111/j.1749-6632.2009.03832.x
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发表时间：
2009-01-01
期刊：
影响因子：
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通讯作者：
Klonisch, Thomas
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文献类型：
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作者：
Bialek, Joanna;Hombach-Klonisch, Sabine;Klonisch, Thomas
胰岛素样肽 3 (INSL3) 存在于过度活跃和肿瘤性甲状腺细胞中，但这种松弛素样肽激素在甲状腺癌发生过程中的功能作用目前尚不清楚。我们建立了表达和分泌生物活性人 INSL3 的人滤泡性甲状腺癌细胞系 FTC-133 稳定转染子的新细胞模型。这些转染子表现出较高的细胞内 ATP 水平，但 INSL3 未能充当生长促进剂。具有局部组织侵袭的侵袭性肿瘤细胞表型的获得代表了许多导致转移的事件的开始，转移是癌症患者致命结果的主要原因。在这里，我们证明了 INSL3 在弹性蛋白降解中的功能，这被认为是肿瘤细胞穿透基底膜和组织侵袭过程中的早期步骤。 INSL3 显着增加了溶酶体酶组织蛋白酶-L 和组织蛋白酶-D 的产生。弹性蛋白分解组织蛋白酶-L 的分泌增强与 FTC-133-INSL3 转染子的弹性蛋白分解活性增加相关。因此，我们提供了第一个证据，证明 INSL3 肽可以通过增强人类甲状腺癌细胞的代谢活性和弹性蛋白降解潜力来促进其早期肿瘤细胞侵袭性。
Insulin-like peptide 3 (INSL3) is present in hyperactive and neoplastic thyrocytes, but the functional role of this relaxin-like peptide hormone during carcinogenesis in the thyroid gland is currently unknown. We generated new cell models of stable transfectants of the human follicular thyroid carcinoma cell line FTC-133 expressing and secreting bioactive human INSL3. These transfectants displayed higher intracenular ATP levels, but INSL3 failed to act as a promoter of growth. The acquisition of an invasive tumor cell phenotype with local tissue invasion represents the beginning of a number of events leading to metastasis, the major cause of fatal outcome in cancer patients. Here we demonstrate a function of INSL3 in elastin degradation, which is considered an early step during basal membrane penetration and tissue invasion by tumor cells. INSL3 markedly increased the production of the lysosomal enzymes cathepsin-L and cathepsin-D. Enhanced secretion of the elastinolytic cathepsin-L was associated with increased elastinolytic activity of FTC-133-INSL3 transfectants. Thus, we provide the first evidence that the INSL3 peptide can promote early tumor cell invasiveness in human thyroid carcinoma cells by enhancing their metabolic activity and elastin-degrading potential.