کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1981798 1539421 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Beneficial role of overexpression of TFPI-2 on tumour progression in human small cell lung cancer
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Beneficial role of overexpression of TFPI-2 on tumour progression in human small cell lung cancer
چکیده انگلیسی


• The Tissue Factor Pathway Inhibitor-2 inhibits small cell lung cancer growth
• Monitoring of small cell lung cancer growth in a mouse orthotopic model by imaging
• Increasing information on the role of TFPI-2 in human lung tumour cells
• Increasing information on TFPI-2 and protease expression in human tissue samples

Tissue factor pathway inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin, a protease which is involved in tumour progression by activating (MMPs). This therefore makes TFPI-2 a potential inhibitor of invasiveness and the development of metastases. In this study, low levels of TFPI-2 expression were found in 65% of patients with small cell lung cancer (SCLC), the most aggressive type of lung cancer. To study the impact of TFPI-2 in tumour progression, TFPI-2 was overexpressed in NCI-H209 SCLC cells which were orthotopically implanted in nude mice. Investigations showed that TFPI-2 inhibited lung tumour growth. Such inhibition could be explained in vitro by a decrease in tumour cell viability, blockade of G1/S phase cell cycle transition and an increase in apoptosis shown in NCI-H209 cells expressing TFPI-2. We also demonstrated that TFPI-2 upregulation in NCI-H209 cells decreased MMP expression, particularly by downregulating MMP-1 and MMP-3. Moreover, TFPI-2 inhibited phosphorylation of the MAPK signalling pathway proteins involved in the induction of MMP transcripts, among which MMP-1 was predominant in SCLC tissues and was inversely expressed with TFPI-2 in 35% of cases. These results suggest that downregulation of TFPI-2 expression could favour the development of SCLC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Open Bio - Volume 3, 2013, Pages 291–301
نویسندگان
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