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Down-regulation of TIMP-1 inhibits cell migration, invasion, and metastatic colonization in lung adenocarcinoma

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Tumor Biology

Abstract

Tissue inhibitor metalloproteinase-1 (TIMP-1) is clinically associated with a poor prognosis for various cancers, but the roles of TIMP-1 in lung cancer metastasis are controversial. Our previous secretomic study revealed that TIMP-1 is highly abundant in high invasiveness cells of lung adenocarcinoma. In the current study, TIMP-1 abundances in primary lung adenocarcinoma tissues, as revealed by immunohistochemistry, are significantly higher in patients with lymph invasion and distant metastasis than in those without. Receiver operating characteristic curve analyses suggest 73.7 and 86.2 % accuracy to separate patients with lymph node and distant metastasis and those without, respectively. Moreover, we demonstrate that the expression level of TIMP-1 positively associates with cell mobility, invasiveness, and metastatic colonization. Most notably, the novel mechanism in which TIMP-1 facilitates metastatic colonization through the mediation of pericellular polyFN1 assembly was revealed. In summary, this study presents novel functions of TIMP-1 in promoting cancer metastasis and suggests TIMP-1 is a potential tissue biomarker for lymph invasion and distant metastasis of lung adenocarcinoma.

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Acknowledgments

This study was supported by Grant MOST103-2113-M-006-003-MY3, MOST102-2325-B-006-003, MOST100-2113-M-006-002-MY3 from the National Science Council. We thank the Tissue Bank, Research Center of Clinical Medicine, National Cheng Kung University Hospital, for preparing the tissue microarray and for providing immunohistochemistry technology. Additionally, we are grateful for the assistance of Dr. Kuen-Jer Tsai and Miss Ya-Chun Hsiao for their services involving TMA image quantification using FACS-like Tissue Cytometry with HistoQuest from Optical Imaging Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital.

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Authors and Affiliations

  1. Institute of Biopharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Ying-Hua Chang & Pao-Chi Liao

  2. Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53706, USA

    Ying-Hua Chang

  3. Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, 70428, Taiwan

    Yi-Jen Chiu, Fang-Ju Liu, Hsiao-Jen Chang & Pao-Chi Liao

  4. Institute of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Hung-Chi Cheng

  5. Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan

    Wu-Wei Lai

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  1. Ying-Hua Chang
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Correspondence to Pao-Chi Liao.

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Ying-Hua Chang and Yi-Jen Chiu contributed equally to this work.

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Chang, YH., Chiu, YJ., Cheng, HC. et al. Down-regulation of TIMP-1 inhibits cell migration, invasion, and metastatic colonization in lung adenocarcinoma. Tumor Biol. 36, 3957–3967 (2015). https://doi.org/10.1007/s13277-015-3039-5

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  • DOI: https://doi.org/10.1007/s13277-015-3039-5

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