1. Using microarray analysis, I identified 14 brain tumor-specific secretory proteins.
2. Of these, only periostin was expressed specifically in malignant tumors.
3. POSTN strongly oriented NSC migration in vitro and in vivo.
4. POSTN powerfully induced the NSC migration using FAK and CDK5 signaling pathway.
5. F3-CD combined with POSTN has strong bystander effect on tumor cell growth
6. Increasing POSTN release clear the scattering glioma cells around the original transplantation site.
70
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81
C6 pNIH3T3
20 40 60 80 100 120
Cell growth (%)
C6 p-NIH3T3
Cell Growth
Cell migration
B A
App. 1. C6 cell growth and migration pattern change by periostin. C6 cells inoculated to low
chamber of boyden chamber and C6 or p-NIH3T3 cell were inoculated to upper chamber. 1 day atter, upper chamber transfer to low chamber and co-cultured for 2 more day. (A) C6 growth pattern is not changed by periostin (upper box). Besides, wound healing ability of C6 cell not induced by periostin (low box). (B) Graph represents quantification of C6 cell number in C6 or p-NIH3T3 cell semi co-culture condition.
82 -국문요약-
사람 뇌종양으로부터 신경줄기세포 굴성 유도물질 동정
아주대학교 대학원의학과 전정용
(지도교수: 이 명 애)
암세포 치료 유전자를 보유하고 있는 줄기세포를 이용한 암치료의 가능성에 대한 보고가 많지만 아직까지 이에 관여하는 인자나 작용 기작에 관해서는 잘 알려있지 않다. 이에 우리는 줄기세포의 굴성을 조절하는 인자와 작용 기작에 관하여 연구하였다. Microarray 분석방법을 통해 암조직에서 과발현되는 유전자들을 확보하였고, 이중 모든 암 조직에서 과발현되고 주변조직으로 분비되는 유전자들을 선별하였다. 이러한 유전자들은 주로 정상조직의 암화에 관련된 유전자들이며 암세포들의 전이과정에도 관여한다.
Periostin은 이러한 유전자중에서 악성종양에서만 강하게 보이는 경향을 보였으며 in vitro 와 in vivo상황에서 줄기세포의 굴성을 강하게 강화시켰다.
또한 줄기세포의 굴성 강화 과정에 있어서 periostin의 수용체인 integrin aVb5 를 이용하여 굴성유도 기작이 시작되었으며 FAK 와 CDK5 하위 신호전달체계를 통하여 세포이동을 강화시킴을 확인하였다. 자살유도 유전자,
83
Cytosine deaminase 를 보유하고 있는 신경줄기세포의 방관자효과를 이용하여 쥐 뇌암 모델에서 암세포성장 억제여부를 확인한 결과, periostin에 의하여 암세포 억제 효과가 강화됨을 관찰하였고 periostin의 양이 증가함에 따라 그
Cytosine deaminase 를 보유하고 있는 신경줄기세포의 방관자효과를 이용하여 쥐 뇌암 모델에서 암세포성장 억제여부를 확인한 결과, periostin에 의하여 암세포 억제 효과가 강화됨을 관찰하였고 periostin의 양이 증가함에 따라 그