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The FVIIa-tissue factor complex induces the expression of MMP7 in LOVO cells in vitro

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

The extracellular interactions of plasma clotting factor VIIa (FVIIa) with tissue factor (TF) on the cell surface trigger intracellular signaling events involved in multiple physiological processes. TF expression is related to the metastatic potential of tumor cells and is a significant risk factor in the development of hepatic metastases in patients with colorectal cancer. At present, it is unclear how the interaction between TF and FVIIa influences the development of metastasis in colon cancer.

Materials and methods

We used a stable LOVO cell line derived from colorectal adenocarcinoma for our model Western blot analysis, Northern blot analysis, polymerase chain reaction, and RNA inference (RNAi), and the Dual-Luciferase Reporter Assay System technology were utilized to determine if MMP7 can be up-regulated by the VIIa/TF complex.

Results

Northern blot analysis confirmed that the plasma clotting factor FVIIa/TF complex resulted in a marked increase in MMP7 expression in a time- and dose-dependent manner via the p38 pathway in vitro. The proximal promoter of the human MMP7 gene was cloned into a luciferase reporter construction (MMP7.luc1592). Upon treatment with FVIIa, reporter activity in LOVO cells was increased by 2.5-fold. TF RNAi almost completely abolished FVIIa-mediated MMP7.luc induction. Deletion constructs from MMP7.luc1592 further defined an active promoter region.

Interpretation

Taken together, these data provide evidence that expression of MMP7 in colon cancer may be regulated by FVIIa and TF at the transcriptional level. MMP7 may act as a downstream mediator of FVIIa/TF signal transduction to facilitate the development of metastasis in colon cancer.

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Acknowledgments

This work was supported by the grants from the National Nature and Science Foundation of China (No.30471683), the Key Project of Chinese Ministry of Education (02003), and the “985” Project Foundation of Peking University.

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Authors and Affiliations

  1. Laboratory of Colon Cancer, First Hospital of Peking University, Peking University, No. 8, Xishiku Street, West District, Beijing, 100034, China

    Jian-Quan Zhang, Yuan-Lian Wan, Yu-Cun Liu, Xin Wang, Jian-Qiang Tang, Tao Wu, Jing Zhu & Yi-Sheng Pan

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  1. Jian-Quan Zhang
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  4. Xin Wang
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Correspondence to Yuan-Lian Wan.

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Zhang, JQ., Wan, YL., Liu, YC. et al. The FVIIa-tissue factor complex induces the expression of MMP7 in LOVO cells in vitro. Int J Colorectal Dis 23, 971–978 (2008). https://doi.org/10.1007/s00384-008-0496-y

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  • DOI: https://doi.org/10.1007/s00384-008-0496-y

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