title: CD7 promotes extramedullary involvement of the B-cell acute lymphoblastic leukemia line Tanoue by enhancing integrin β2-dependent cell adhesiveness.
abstract: Extramedullary involvement (EMI) is a factor that defines prognosis of acute lymphoblastic leukemia; however, the molecular mechanism(s) remain elusive. Here, we show that CD7 promotes EMI of the human B-cell acute lymphoblastic leukemia cell line Tanoue. The Tanoue cell line expressing firefly luciferase, Luc-Tanoue, was transplanted into non-obese diabetic/severe combined immunodeficient mice, and cells infiltrated into the brain were cultured ex vivo. This process was repeated 4 times to obtain the highly invasive line Luc-Tanoue-F4. Comparison of the global gene expression signatures of Luc-Tanoue-F4 and Luc-Tanoue indicated that the CD7 gene showed the largest increase in expression among EMI-related genes in Luc-Tanoue-F4 cells. Overexpression of CD7 in Tanoue enhanced cell invasiveness. Among cell migration, proliferation, adhesion and protease activity, only cell adhesiveness showed enhancement in Luc-Tanoue-F4. Expression of the intracellular domain, but not the extracellular domain, of CD7 enhanced cell adhesiveness. Luc-Tanoue-F4 showed a higher level of integrin β2 expression; overexpression of CD7 induced the expression of integrin β2 in Luc-Tanoue. These results show that CD7 induces integrin β2 and enhances cell adhesiveness and invasiveness in Tanoue cells. This study highlights the role of the CD7/integrin β2 axis as a critical pathway in the process of EMI of human B-cell acute lymphoblastic leukemia.
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondoh
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Kageaki
authors.initials: K
authors.lastname: Kuribayashi
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Yanagihara
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009374:Neoplasms, Experimental; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology*
chemical_list: D018821:CD18 Antigens