Hosokawa Kentaro, Arai Fumio, Yoshihara Hiroki, Nakamura Yuka, Gomei Yumiko, Iwasaki Hiroko, Miyamoto Kana, Shima Haruko, Ito Keisuke, Suda Toshio
Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
Biochem Biophys Res Commun. 2007 Nov 23;363(3):578-83. doi: 10.1016/j.bbrc.2007.09.014. Epub 2007 Sep 18.
During postnatal life, the bone marrow (BM) supports both self-renewal and differentiation of hematopoietic stem cells (HSCs) in specialized niches, such as osteoblastic niche and vascular niche. A cell adhesion molecule, N-cadherin expressed in the HSCs and osteoblasts, suggesting that homophylic binding of N-cadherin induce the adhesion of HSCs to the niche cells. Here we demonstrate that an anti-cancer drug, 5-fuluorouracil induces reactive oxygen species (ROS) in HSCs, which suppressed N-cadherin expression. These events result in the shift of side population (SP) cells to non-SP cells, indicating that quiescent HSCs are detached from the niche. Administration of a potent anti-oxidant, N-acetyl cystein (NAC) suppressed the shift from SP cells. These data suggest that ROS suppressed the N-cadherin-mediated cell adhesion, and induce the exit of HSCs from the niche.
在出生后的生命过程中，骨髓（BM）在诸如成骨细胞龛和血管龛等特殊微环境中支持造血干细胞（HSCs）的自我更新和分化。一种细胞粘附分子N-钙粘蛋白在造血干细胞和成骨细胞中表达，这表明N-钙粘蛋白的同源性结合诱导造血干细胞与龛细胞的粘附。在这里，我们证明一种抗癌药物5-氟尿嘧啶在造血干细胞中诱导活性氧（ROS），从而抑制N-钙粘蛋白的表达。这些事件导致侧群（SP）细胞向非SP细胞转变，表明静止的造血干细胞从龛中脱离。给予一种有效的抗氧化剂N-乙酰半胱氨酸（NAC）可抑制从SP细胞的转变。这些数据表明，活性氧抑制了N-钙粘蛋白介导的细胞粘附，并诱导造血干细胞从龛中退出。
