Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Chemotherapeutic Drug Resistant Cancer Stem-like Cells of Glioma

다형성 교모세포종의 항생제 내성 종양 줄기세포

  • Kang, Mi-Kyung (Department of Physiology, College of Medicine, Pusan National University) ;
  • Kang, Soo-Kyung (Department of Physiology, College of Medicine, Pusan National University)
  • Published : 2007.08.30
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Abstract

Glioblastoma multiforme (GBM) is the most frequently occurring brain cancer. Although the existence of cancer stem cells (CSCs) in GBM has been established, there is little evidence to explain the link between CSCs and chemoresistance. In this study, we investigated that only a few cells of A172 and established GBM2 survived after 1,3-bis(2chloroethyl)-1-nitrosourea (BiCNU) exposures and these sur-vived cells resist the subsequent BiCNU treatment. In addition, these BiCNU-resistant small pop-ulations derived from GBM cells increased the phosphorylations of Erk and Akt and highly expressed CD133 stem cell surface marker. Furthermore, we observed that the BiCNU-resistant cancer cells de-rived from GBM have grown tumors when transplanted into severe combined immuno-deficient (SCID) mouse brain. These results demonstrate that BiCNU-resistant subpopulation cells derived from GBM have cancer stem-like cell properties. Therefore, it may provide provide further evidence that CSCs in GBM have chemotherapeutic drug resistance.

다형성 교모세포종은 뇌종양 가운데 가장 빈번하게 발병하는 악성종양이다. 다형성 교모세포종에 종양 줄기세포가 존재한다는 보고가 있음에도 불구하고, 항암제 내성과 종양 줄기세포 사이의 상호 연관성에 관한 연구는 아직 미비한 실정이다. 본 연구에서 다형성 교모세포종 세포주 A172 및 뇌종양 환자로부터 확립한 GBM2에 1,3-bis(2 -chloroethyl)-1-nitrosourea (BiCNU)를 처리시 극소량의 세포군만이 생존하며, 이들 생존 세포군은 BiCNU 재처리에 내성을 나타내는 것으로 조사되었다. 또한 이 다형성 교모세포종 유래 BiCNU-내성세포군의 Erk 및 Akt 인산화 활성이 증가되었으며, CD133 줄기세포 표지인자를 발현하는 세포가 다량 존재하였다. 이와 아울러, 다형성 교모세포종 유래 BiCNU-내성세포를 severe combined immuno-deficient (SCID) mouse brain에 이식하였을 때 암이 형성되는 것을 관찰할 수 있었다. 이와 같은 결과는 다형성 교모세포종 유래 BiCNU-내성세포가 종양줄기세포의 능력을 가지는 것으로 생각된다. 따라서 이상의 결과는 다형성 교모세포종에 존재하는 종양줄기세포가 항암제 내성에 관여 한다는 중요한 단서를 제공해줄 수 있을 것으로 사료된다.

Keywords

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