방사선종양학

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  • [Radiother Oncol.] A hepatocyte growth factor/MET-induced antiapoptotic pathway protects against radiation-induced salivary gland dysfunction.간세포생장인자(HGF)/MET-유도 항세포자멸경로의 방사선유발 침샘기능장애에 대한 보호 작용

    연세의대 / 윤여준, 임재열*

  • 출처
    Radiother Oncol.
  • 등재일
    2019 Sep
  • 저널이슈번호
    138:9-16. doi: 10.1016/j.radonc.2019.05.012. Epub 2019 May 25.
  • 내용

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    Abstract
    OBJECTIVE:
    Hepatocyte growth factor (HGF) and its receptor MET are expressed in the salivary glands during developmental stages and tumor formation; however, the function of HGF in injured salivary gland tissues remains unclear. The present study investigated the role of HGF in protecting the salivary glands against radiation-induced injury using an organotypic culture method.

    MATERIALS AND METHODS:
    Acinar-like organoids were formed by means of a three-dimensional (3D) human parotid tissue-derived spheroids (hPTS) culture method. Radioprotective effects of HGF on irradiated hPTS and signaling pathways on radioprotection were investigated.

    RESULTS:
    We detected MET expression in hPTS grown in a 3D culture. Treatment of irradiated hPTS with recombinant human HGF (rhHGF) restored salivary marker expression and secretory function of hPTS. Changes in the phosphorylation levels of apoptosis-related proteins through HGF-MET axis inhibited radiation-induced apoptosis. Treatment with PHA665752, a MET inhibitor, blocked MET-PI3K-AKT pathway, increased apoptosis, and suppressed the radioprotective effect of rhHGF against IR-induced damage of hPTS.

    CONCLUSIONS:
    These results suggest that HGF is a key effector of radioprotection and that HGF-MET-PI3K-AKT axis is involved in protecting the salivary glands from radiation-induced apoptosis.

     


    Author information

    Yoon YJ1, Shin HS1, Lim JY2.
    1
    Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
    2
    Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: jylimmd@yuhs.ac.

  • 키워드
    Hepatocyte growth factor; Radiation; Salivary gland; Three-dimensional cell culture
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