Format

Send to

Choose Destination
Sci Rep. 2018 Nov 21;8(1):17174. doi: 10.1038/s41598-018-33873-2.

Pre-B acute lymphoblastic leukemia expresses cell surface nucleolin as a 9-O-acetylated sialoglycoprotein.

Author information

1
Department of Systems Biology, Beckman Research Institute, City of Hope, Monrovia, CA, USA.
2
Department of Microbiology and Immunology, Baker Institute for Animal Health and Feline Health Center, Cornell University, Ithaca, NY, USA.
3
Section of Molecular Carcinogenesis, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, CA, USA.
4
University of California, Los Angeles, CA, 90095, USA.
5
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
6
Division of Hematology/Oncology and Bone Marrow Transplant, Children's Hospital Los Angeles, Los Angeles, CA, USA.
7
Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
8
Department of Systems Biology, Beckman Research Institute, City of Hope, Monrovia, CA, USA. eheisterkamp@coh.org.
9
Division of Hematology/Oncology and Bone Marrow Transplant, Children's Hospital Los Angeles, Los Angeles, CA, USA. eheisterkamp@coh.org.
10
Departments of Pediatrics and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. eheisterkamp@coh.org.

Abstract

Precursor B acute lymphoblastic leukemias (pre-B ALLs) abnormally express a specific glycan structure, 9-O-acetylated sialic acid (9-O-Ac-Sia), on their cell surface, but glycoproteins that carry this modification have not been identified. Using three different lectins that specifically recognize this structure, we establish that nucleolin (NCL), a protein implicated in cancer, contains 9-O-Ac-Sia. Surprisingly, antibodies against the glycolipid 9-O-Ac-Sia GD3 also detected 9-O-Ac-Sia NCL. NCL is present on the surface of pre-B ALL cells as a sialoglycoprotein that is partly 9-O-acetylated and conversely, 9-O-Ac-Sia-containing structures other than NCL are present on these cells as well. Interestingly, NCL and the 9-O-Ac-Sia signal had less co-localization on normal pre-B cells. We also investigated regulation of NCL on the cell surface and found that sialidase treatment increased the percentage of cells positive for cell surface NCL, suggesting that sialylation of NCL promotes internalization. Treatment of pre-B ALL cells with the chemotherapy drug vincristine also increased the percentage of cells with surface NCL and correlated with increased 9-O-Ac-Sia expression. All tested leukemia cells including primary samples expressed NCL, suggesting it as a possible therapeutic target. We confirmed this by showing inhibition of cell proliferation in some pre-B ALLs by exposure to a NCL-specific aptamer AS1411.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center