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CD43, but not P-Selectin Glycoprotein Ligand-1, Functions as an E-Selectin Counter-Receptor in Human Pre-B–Cell Leukemia NALL-1

¹ Cell Regulation Analysis Team, Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology; ² Function of Biomolecule, University of Tsukuba, Tsukuba, Japan; ³ Core Research for Evolution Science and Technology of Japan Science and Technology Agency, Kawaguchi, Japan; ⁴ Department of Developmental Biology, National Research Institute of Child Health and Development, Tokyo, Japan; ⁵ The Department of Molecular Pathology, Aichi Cancer Center, Chikusa-ku, Nagoya, Japan; and ⁶ Division of Cell Transplantation and Transfusion and ⁷ Division of Stem Cell Regulation, Jichi Medical School, Shimotsuke, Tochigi, Japan

Requests for reprints: Mitsuru Nakamura, Cell Regulation Analysis Team, Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Central-2, 1-1-1 Umezono, Tsukuba 305-8568, Japan. Phone: 81-29-861-2745; Fax: 81-29-861-2744; E-mail: owl.nakamura{at}aist.go.jp.

Key Words: Pre-B leukemia • Selectin ligand • Sialomucin • Extramedullar infiltration/tissue infiltration • Cancer stem cells

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 -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. [Cancer Res 2008;68(3):790–9]