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Pre-existing fas ligand (FasL) in cancer cells elicits tumor-specific protective immunity, but delayed induction of FasL expression after inoculation facilitates tumor formation

Authors

  • Hsiao-Ying Chiu,

    1. Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology (CMBB), National Taiwan Ocean University, Keelung, Taiwan, ROC
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  • Guang-Huan Sun,

    1. Division of Urology, Department of Surgery, Tri-service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
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  • Shiow-Yi Chen,

    1. Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology (CMBB), National Taiwan Ocean University, Keelung, Taiwan, ROC
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  • Hsiao-Hsien Wang,

    1. Section of Urology, Cheng-Hsin Rehabilitation Medical Center, Taipei, Taiwan, ROC
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  • Ming-Yi Ho,

    1. Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University and Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, ROC
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  • Chia-Yi Chu,

    1. Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology (CMBB), National Taiwan Ocean University, Keelung, Taiwan, ROC
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  • Wan-Lin Wu,

    1. Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology (CMBB), National Taiwan Ocean University, Keelung, Taiwan, ROC
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  • Ren-Shiang Jhou,

    1. Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology (CMBB), National Taiwan Ocean University, Keelung, Taiwan, ROC
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  • Yi-Lin Tsai,

    1. Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology (CMBB), National Taiwan Ocean University, Keelung, Taiwan, ROC
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  • Rui-Ting Huang,

    1. Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology (CMBB), National Taiwan Ocean University, Keelung, Taiwan, ROC
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  • Kuang-Hui Sun,

    Corresponding author
    1. Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University and Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, ROC
    • Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
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  • Shye-Jye Tang

    Corresponding author
    1. Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology (CMBB), National Taiwan Ocean University, Keelung, Taiwan, ROC
    • Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan, ROC.
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Abstract

Overexpression of Fas ligand (FasL) in cancer cells elicits potential antitumor effects via recruitment of neutrophils. Conversely, FasL-expressing tumors may counterattack tumor-infiltrating lymphocytes by delivering apoptotic death signals via Fas/FasL interactions, which may lead to tumor escape. In order to distinguish the role of FasL in antitumor activity and tumor progression, Lewis lung carcinoma cells (LLC-1) were used to establish the cell line LLC-FasL, in which FasL expression was repressed by doxycycline (Dox) treatment and induced in the absence of Dox. LLC-FasL cells promote tumor regression when expressing FasL, whereas tumor outgrowth is observed by depletion of FasL expression. To investigate whether initial expression of FasL during tumor formation is critical for FasL-mediated tumor regression, Dox-treated LLC-FasL cells were inoculated into Dox-treated mice, but Dox treatment was stopped 5 days after inoculation. When low cell numbers were inoculated, we observed 80% survival and no tumor formation, whereas no mice survived inoculation with high cell numbers, despite the delayed induction of FasL by Dox withdrawal. The inoculation of a high density of cells may establish a favorable tumor microenvironment before the expression of FasL. Our findings demonstrate that FasL may elicit antitumor activity when it is initially present on injected cancer cells and thus can act prior to tumor microenvironment formation. Furthermore, a well-established tumor microenvironment abrogates FasL-mediated antitumor activity. © 2012 Wiley Periodicals, Inc.

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