Inhibition effect of propargylglycine on human fibrosarcoma HT-1080 cell invasiveness.

Cancer biochemistry biophysics Pub Date : 1998-06-01
A Haga, H Nagase, H Kito, T Sato
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Abstract

Effect of propargylglycine (2-Amino-4-pentynoic acid, PPG) on invasive property of human fibrosarcoma HT-1080 cell was investigated. PPG treatment of HT-1080 significantly reduced the total cellular metallothioneins (MTs) contents, and the resistance of HT-1080 against heavy metals toxicity decreased with the decrease of the MTs contents. The HT-1080 cell invasion to reconstituted basement membrane Matrigel (MG) was inhibited by the PPG treatment in a PPG concentration-dependent fashion. The inhibition was due to the lowering of HT-1080 cells attachment to MG and degradation activity of matrix metalloproteinases (MMPs) secreted from HT-1080 by the PPG treatment. However, the chemotactic ability of the PPG treated HT-1080 was enhanced. Our results suggest that MTs concentration levels in a malignant tumor cell are closely related to its invasiveness, and if MTs level of tumor cell can be controlled, cancer metastasis may be able to be controlled.

丙基甘氨酸对人纤维肉瘤HT-1080细胞侵袭性的抑制作用
研究了丙基甘氨酸(2-氨基-4-戊酸,PPG)对人纤维肉瘤HT-1080细胞侵袭性的影响。PPG处理显著降低了HT-1080细胞总金属硫蛋白(mtts)含量,且随着mtts含量的降低,HT-1080对重金属毒性的抗性降低。PPG抑制HT-1080细胞对重组基膜基质(MG)的侵袭,并呈浓度依赖性。这种抑制作用是由于PPG处理降低了HT-1080细胞对MG的附着和HT-1080分泌的基质金属蛋白酶(MMPs)的降解活性。然而,PPG处理HT-1080的趋化能力增强。我们的研究结果表明,恶性肿瘤细胞中MTs的浓度水平与其侵袭性密切相关,如果能控制肿瘤细胞中MTs的水平,就有可能控制肿瘤的转移。
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