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 ;-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]

RNA-seq Transcriptional Profiling of Peripheral Blood Leukocytes from Cattle Infected with Mycobacterium bovis

“…The Leukocyte Extravasation Signaling pathway exhibited a decrease in expression for many genes encoding positive modulators of this pathway, including SPN (also known as CD43 ), ITGAL, ITGB2 , and PECAM1 (52–55). Leukocyte extravasation refers to the transendothelial migration of activated leukocytes from the blood into infected tissue and is vital for immune surveillance and defense (56).…”

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

“…A critical event of metastatic dissemination to distant sites is the adhesion of circulating malignant cells to vascular endothelial cells [95]. Many studies point to a role for E-selectin displayed on vascular endothelial cells in the recruitment of tumor cells to metastatic sites in breast, bladder, gastric, pancreatic, and colorectal carcinoma, as well as hematological malignancies [95,106,107]. Interestingly, PODXL has been implicated in the interaction of tumor cells to E-selectin as well as to L-selectin [34].…”

The Novel Orally Active Proteasome Inhibitor K-7174 Exerts Anti-myeloma Activity in Vitro and in Vivo by Down-regulating the Expression of Class I Histone Deacetylases

“…A mutation was inserted at nucleotide position 322 (G/A) by PCR-based site-directed mutagenesis. Wild-type and mutated PSMB5 cDNAs were inserted into the lentiviral vector CSII-CMV-MCS-IRES-VENUS (kindly provided by Dr. Hiroyuki Miyoshi, RIKEN BioResource Center, Ibaraki, Japan) (26), and co-transfected into 293FT cells with packaging plasmids (Invitrogen) to produce infective lentiviruses in culture supernatants (27). RPMI8226 cells were infected by each viral supernatant for 24 h. We collected VENUS-positive cells by a FACSaria flow cytometer, seeded 1 cell/well in a 96-well plate to obtain single cell clones.…”