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Enhanced constitutive invasion activity in human nontumorigenic keratinocytes exposed to a low level of barium for a long time

Authors

  • Nguyen D. Thang,

    1. Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, Japan
    2. Department of Biochemistry and Plant Biology, Vietnam National University, Hanoi, Vietnam
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  • Ichiro Yajima,

    1. Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, Japan
    2. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan
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  • Shoko Ohnuma,

    1. Voluntary Body for International Health Care in Chubu University, Kasugai, Aichi, Japan
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  • Nobutaka Ohgami,

    1. Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, Japan
    2. Voluntary Body for International Health Care in Chubu University, Kasugai, Aichi, Japan
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  • Mayuko Y. Kumasaka,

    1. Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, Japan
    2. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan
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  • Gaku Ichihara,

    1. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan
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  • Masashi Kato

    Corresponding author
    1. Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, Japan
    2. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan
    3. Voluntary Body for International Health Care in Chubu University, Kasugai, Aichi, Japan
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  • Supported by: Ministry of Education, Culture, Sports, Science and Technology (MEXT) (Grants-in-Aid for Scientific Research [B], Nos. 20406003, 24390157, and 24406002; Grant-in-Aid for Challenging Exploratory Research, No. 23650241; Grant-in-Aid for Scientific Research on Innovative Areas, No. 24108001); MEXT and Chubu University (COE Project [Health Science Hills] for Private Universities, No. S0801055); Supported by: Japan Society for the Promotion of Science (JSPS [AA Science Platform Program]); Tokyo Biochemical Research Foundation; the Naito Foundation Natural Science Scholarship; the Uehara Memorial Foundation; AEON Environmental Foundation; The Cosmetology Research Foundation.

ABSTRACT

We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 161–167, 2015.

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