title: CD43, but not P-selectin glycoprotein ligand-1, functions as an E-selectin counter-receptor in human pre-B-cell leukemia NALL-1.
abstract: B-cell precursor acute lymphoblastic leukemia (BCP-ALL/B-precursor ALL) is characterized by a high rate of tissue infiltration. The mechanism of BCP-ALL cell extravasation is not fully understood. In the present study, we have investigated the major carrier of carbohydrate selectin ligands in the BCP-ALL cell line NALL-1 and its possible role in the extravascular infiltration of the leukemic cells. B-precursor ALL cell lines and clinical samples from patients with BCP-ALL essentially exhibited positive flow cytometric reactivity with E-selectin, and the reactivity was significantly diminished by O-sialoglycoprotein endopeptidase treatment in NALL-1 cells. B-precursor ALL cell lines adhered well to E-selectin but only very weakly to P-selectin with low-shear-force cell adhesion assay. Although BCP-ALL cell lines did not express the well-known core protein P-selectin glycoprotein ligand-1 (PSGL-1), a major proportion of the carbohydrate selectin ligand was carried by a sialomucin, CD43, in NALL-1 cells. Most clinical samples from patients with BCP-ALL exhibited a PSGL-1(neg/low)/CD43(high) phenotype. NALL-1 cells rolled well on E-selectin, but knockdown of CD43 on NALL-1 cells resulted in reduced rolling activity on E-selectin. In addition, the CD43 knockdown NALL-1 cells showed decreased tissue engraftment compared with the control cells when introduced into gamma-irradiated immunodeficient mice. These results strongly suggest that CD43 but not PSGL-1 plays an important role in the extravascular infiltration of NALL-1 cells and that the degree of tissue engraftment of B-precursor ALL cells may be controlled by manipulating CD43 expression.
authors.affiliation: Cell Regulation Analysis Team, Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan
authors.forename: Chizu
authors.initials: C
authors.lastname: Nonomura
authors.forename: Jiro
authors.initials: J
authors.lastname: Kikuchi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ozaki
authors.forename: Kanae
authors.initials: K
authors.lastname: Mitsunaga
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Ando
authors.forename: Akiko
authors.initials: A
authors.lastname: Kanamori
authors.forename: Reiji
authors.initials: R
authors.lastname: Kannagi
authors.forename: Junichiro
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Muroi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D019040:E-Selectin / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D051917:Leukosialin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019007:P-Selectin / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D052116:Sialomucins / Q000378:metabolism; D014162:Transfection
chemical_list: D019040:E-Selectin; D051917:Leukosialin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D034741:RNA, Small Interfering; C465014:SPN protein, human; D052116:Sialomucins