脳腫瘍における腫瘍幹細胞 (Cancer Stem Cell) の存在

Cancer Stem Cell in Pediatric Brain Tumor

　Ⅰ．はじめに

　近年，いくつかの臓器由来の悪性腫瘍から腫瘍幹細胞（cancer stem cell）が単離されたとの報告が相次いでいる^1,2,5)．腫瘍幹細胞とは，腫瘍内で自己複製し，かつ様々な種類の分化細胞を生じ二次腫瘍を形成する元となる細胞である．

　頭蓋内腫瘍では，神経膠腫や髄芽腫などの小児脳腫瘍と神経幹細胞（neural progenitor cells）との類似は以前より示唆されてきた⁹⁾が，最近，ある種の小児脳腫瘍に腫瘍幹細胞が存在するとの報告がわれわれを含む複数のグループから提出された^5,10)．以下，腫瘍幹細胞に関する最近の知見とその臨床的意義について論ずる．

　Cancers are formed by heterogeneous cell types from immature highly proliferative cells to lineage-committed differentiated cells. Transplantation studies have suggested the existence of "cancer stem cells",individual cells capable of producing an entire tumor.

　Recent advances in stem cell research have allowed for the demonstration of the existence of cancer stem cells in acute myeloid leukemia,breast cancer,and,most recently,in pediatric brain tumors. Each of these has some similarities with the normal stem cells in the corresponding organs. For example,leukemia stem cells express some,but not all,markers of hematopoietic stem cells. Regarding pediatric brain tumors,putative cancer stem cells were identified from medulloblastoma and also from glioma. These tumor-derived cells self-renew under clonal conditions,and differentiate into neurons and glia as well as into abnormal cells with mixed phenotypes. Interestingly,the tumor stem/progenitors,enriched in culture,maintained proliferation after 4 weeks from transplantation into neonatal rat brain. In this review,we discuss the difference as well as the similarity between tumor and normal stem cells,and also the possible clinical implication of cancer stem cells.