title: Role of stromal cells-mediated Notch-1 in the invasion of T-ALL cells.
abstract: Extra-medullary infiltration is still one of the main causes of recurrence and treatment failure of T-cell acute lymphoblastic leukemia (T-ALL). Intensive studies revealed that Notch pathway plays an important role in the invasion of tumor cells. Notch pathway can be triggered by binding of Notch receptors on T-ALL cells to their ligands on bone marrow stromal cells (BMSCs), which contributes to the development of T-ALL. However, the effect and molecular mechanisms of BMSCs in invasion of T-ALL cells remain unclear. To explore the effect of Notch-1 on the invasiveness of T-ALL cells, we co-cultured T-ALL cells with BMSCs (from healthy donors)/BMSCs(⁎) (from newly diagnosed T-ALL patients). The results demonstrated that BMSCs/BMSCs(⁎) promoted invasion of T-ALL cells through activating Notch-1 signaling. In particular, T-ALL cells showed a higher invasive potential in the presence of BMSCs(⁎) than BMSCs. Knockdown of Notch-1 prevented the positive effect of stromal cells-mediated invasion. Our study also showed that BMSCs/BMSCs(⁎)-induced Notch-1 activation increased the expression of matrix metalloprote inase-2 (MMP-2) and matrix metalloprote inase-9 (MMP-9), which increased invasiveness. These results provided theoretical and laboratory basis for the prevention and treatment of extra-medullary infiltration of T-ALL cells.
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China.
authors: Congcong
authors: C
authors: Yin
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China.
authors: Jingjing
authors: J
authors: Ye
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China.
authors: Jie
authors: J
authors: Zou
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China.
authors: Ting
authors: T
authors: Lu
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China.
authors: Yahui
authors: Y
authors: Du
authors: School of Information Science and Engineering, Shandong University, Jinan, China.
authors: Zhi
authors: Z
authors: Liu
authors: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China.
authors: Rong
authors: R
authors: Fan
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China.
authors: Fei
authors: F
authors: Lu
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China.
authors: Peng
authors: P
authors: Li
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China.
authors: Daoxin
authors: D
authors: Ma
authors: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Road, Jinan 250012, China. Electronic address: jichunyan@sdu.edu.cn.
authors: Chunyan
authors: C
authors: Ji
mesh_terms: D002465:Cell Movement; D018920:Coculture Techniques; D055785:Gene Knockdown Techniques; D006801:Humans; D019169:Jurkat Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D051881:Receptor, Notch1 / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: BMSCs; Co-culture; Invasion; Notch-1; T-ALL