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EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2

Cancer Gene Therapy volume 21, pages 246–255 (2014)Cite this article

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Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN) exhibits overexpression in various cancers and promotes cancer progression and metastasis via the interaction with its associated molecules. The scFv-M6-1B9 intrabody has a potential ability to reduce EMMPRIN cell surface expression. However, the subsequent effect of scFv-M6-1B9 intrabody-mediated EMMPRIN abatement on its related molecules, α3β1-integrin, MCT1, MMP-2 and MMP-9, is undefined. Our results demonstrated that the scFv-M6-1B9 intrabody efficiently decreased α3β1-integrin cell surface expression levels. In addition, intracellular accumulation of MCT1 and lactate were increased. These results lead to suppression of features characteristic for tumor progression, including cell migration, proliferation and invasion, in a colorectal cancer cell line (Caco-2) although there was no difference in MMP expression. Thus, EMMPRIN represents an attractive target molecule for the disruption of cancer proliferation and metastasis. An scFv-M6-1B9 intrabody-based approach could be relevant for cancer gene therapy.

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Acknowledgements

This work was supported by the Discovery-based Development Grant, Research Chair Grant from the National Sciences and Technology Development Agency (NSTDA), Thailand, the Thailand Research Fund (TRF) and the National Research University project under the Thailand Office of the Commission on Higher Education, Thailand. We thank Prof. André Lieber from the Division of Medical Genetics, University of Washington, Seattle, USA, for providing Ad5/F35 vector and Associate Professor Suchart Kothan from the Department of Radiologic Technology, Chiang Mai University, for his advice on NMR spectral analysis.

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Authors and Affiliations

  1. Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

    S Sangboonruang, P Thammasit & K Tragoolpua

  2. Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

    N Intasai

  3. Department of Medical Technology, Clinical Immunology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

    W Kasinrerk & C Tayapiwatana

  4. Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

    W Kasinrerk & C Tayapiwatana

  5. BioMedical Engineering Center, Chiang Mai University, Chiang Mai, Thailand

    C Tayapiwatana

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Correspondence to K Tragoolpua.

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Sangboonruang, S., Thammasit, P., Intasai, N. et al. EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2. Cancer Gene Ther 21, 246–255 (2014). https://doi.org/10.1038/cgt.2014.24

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