RRC ID 38296
著者 Funayama K, Saito-Kurimoto Y, Ebihara Y, Shimane M, Nomura H, Tsuji K, Asano S.
タイトル Adhesion-mediated self-renewal abilities of Ph+ blastoma cells.
ジャーナル Biochem Biophys Res Commun
Abstract The Philadelphia chromosome-positive blastoma, maintained by serial subcutaneous transplantation in nude mice, is a highly proliferating biological mass consisting of homogenous CD34(+)CD38(-) myeloblastoid cells. These cells newly evolved from pluripotent leukemia stem cells of chronic myeloid leukemia in the chronic phase. Therefore, this mass may provide a unique tool for better understanding cellular and molecular mechanisms of self-renewal of leukemia stem cells. In this paper, we demonstrated that intravenously injected blastoma cells can cause Ph+ blastic leukemia with multiple invasive foci in NOD/SCID mice but not in nude mice. In addition, using an in vitro culture system, we clearly showed that blastoma cell adhesion to OP9 stromal cells accelerates blastoma cell proliferation that is associated with up-regulation of BMI1 gene expression; increased levels of beta-catenin and the Notch1 intra-cellular domain; and changed the expression pattern of variant CD44 forms, which are constitutively expressed in these blastoma cells. These findings strongly suggest that adhesion of leukemic stem cells to stromal cells via CD44 might be indispensable for their cellular defense against attack by immune cells and for maintenance of their self-renewal ability.
巻・号 396(2)
ページ 193-8
公開日 2010-5-28
DOI 10.1016/j.bbrc.2010.03.172
PII S0006-291X(10)00647-9
PMID 20362549
MeSH Animals Cell Adhesion Cell Culture Techniques Gene Expression Regulation, Leukemic Humans Hyaluronan Receptors / genetics Hyaluronan Receptors / metabolism Mice Mice, Inbred NOD Mice, SCID Neoplasm Transplantation Neoplastic Stem Cells / pathology* Nuclear Proteins / genetics Pluripotent Stem Cells / pathology* Polycomb Repressive Complex 1 Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology* Proto-Oncogene Proteins / genetics Receptor, Notch1 / metabolism Repressor Proteins / genetics beta Catenin / metabolism
IF 2.985
引用数 3
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 OP9(RCB1124)