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Matrilysin inhibits proliferation and modulates sensitivity of lung cancer cells to FasL-mediated apoptosis

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Abstract

Aims and background Matrix metalloproteinase (MMP) family member MMP-7 (matrilysin) cleaves various cell-surface proteins to alter their effector functions in addition to a broad substrate specificity against extracellular matrix components. Matrilysin expression is closely associated with the advanced clinicopathological stages and unfavorable prognosis. The current study tried to describe the comprehensive impacts of matrilysin on proliferation, and focused on its influence on the susceptibility to FasL-induced apoptosis in A549 lung adenocarcinoma cell line. We also detected the expressions of apoptosis-relative genes to further clarify the underlying mechanisms. Study design The viability of A549 cells was determined by MTT and the apoptosis was assessed by Hoechst 33342 staining and Annexin V-FITC/PI apoptosis kit. The expressions of apoptosis-relative genes were evaluated by flow cytometry, ELISA, and real-time quantitative RT-PCR, respectively. Results Overall, matrilysin exhibited the inhibition of cell growth in a dose- and time-dependent manner by arresting in G0/G1 phase of the cell cycle and inducing apoptosis on A549 cells. Although it directly promoted apoptosis at high concentrations, a certain range of matrilysin might protect tumor cells from FasL-mediated death. The underlying mechanism may be due to the imbalance in the susceptibility of surface membrane-bound Fas receptor and ligand to proteolysis activity of matrilysin. Conclusion Our data indicated matrilysin may be multiple, multifarious, and multifaceted functions contributing to early tumor growth. A therapeutic key might be to modulate activity and function of matrilysin under diverse pathological conditions, but not completely eliminate the expression or function.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Pulmonary and Critical Care, The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Street, Guangzhou, 510630, China

    Hui Liu, Jing Huang, Benquan Wu, Yuqi Zhou, Jiaxin Zhu & Tiantuo Zhang

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  1. Hui Liu
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  2. Jing Huang
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  3. Benquan Wu
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  4. Yuqi Zhou
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  5. Jiaxin Zhu
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  6. Tiantuo Zhang
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Correspondence to Tiantuo Zhang.

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Liu, H., Huang, J., Wu, B. et al. Matrilysin inhibits proliferation and modulates sensitivity of lung cancer cells to FasL-mediated apoptosis. Med Oncol 25, 419–430 (2008). https://doi.org/10.1007/s12032-008-9057-z

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  • DOI: https://doi.org/10.1007/s12032-008-9057-z

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