Changes in expression of the cell adhesion molecule PECAM‐1 (CD31) during differentiation of human leukemic cell lines

Abstract

in expression of the cell adhesion molecule PECAM-1 (CD3 1) during differentiation of human leukemic cell lines.Abstract: PECAM-I, a member of the immunoglobulin gene superfamily, is widely distributed on cells of the vascular system, and mediates cellular interactions through both homotypic and heterotypic adhesive mechanisms. Previous studies have demonstrated that PECAM-I is initially expressed at high levels on CD34+ multipotential progenitors in the bone marrow, but is subsequently downregulated in more committed precursors of all lineages. Interestingly, although PECAM-1 expression is high on circulating monocytes and neutrophik, little is known about the upregulation of PECAM-1 expression during terminal myelomonocytic differentiation. We have further characterized this process by examining PE-CAM-I expression during chemically-induced differentiation' of the U937, HL-60 and HEL cell lines. Quantitative Western blot analysis of cellular lysates indicated that PECAM-1 expression could be upregulated in U937 and HL-60 cells by phorbol esters or dimethyl sulfoxide. Northern blot analysis showed that PECAM-I mRNA levels appeared to increase in parallel with that of PECAM-1 protein. We also observed a marked difference in the apparent molecular mass of PECAM-1 that was lineage-specific, both in differentiated leukemic cell lines and in their corresponding leukocyte population. Immunofluorescence localization indicated that the cellular distribution of PECAM-1 in U937 and HL-60 cells was similar to that of their normal circulating counterparts, and that the pattern of distribution again displayed lineage fidelity. The ability to induce the expression of PECAM-1 molecules having different glycosylation and surface expression patterns may prove useful for further elucidation of the role of PECAM-1 in hematopoiesis, as well as studies of the cell lineage-I specific modulation of PECAM-1 function.

Identification of a Functional NF-κB Site in the Platelet Endothelial Cell Adhesion Molecule-1 Promoter

“…In addition, phorbol esters can be used in vitro as nonphysiological activators of NF-B. Previous studies have demonstrated that PECAM-1 expression is up-regulated upon treatment of monocytic cell lines with phorbol esters (16,22,23), a finding compatible with the involvement of NF-B on PECAM-1 expression. This and the existence of two consensus NF-B sites at ϩ110 and Ϫ409 within the promoter region led us to assess the possible involvement of NF-B on PECAM-1 expression.…”

“…Endothelial cells express constitutively high levels of PECAM-1, while its expression is regulated in monocytes, during the process of maturation and differentiation to macrophages (16,22,23). The results here presented suggest that part of this regulation in macrophages is mediated through the NF-B factor, active at the ϩ110/ϩ120 site of the PECAM-1 promoter used in this study.…”

“…Structural characterization of the PECAM-1 promoter region revealed consensus sites for nuclear factors of the NF-B family. Because PECAM-1 expression is up-regulated upon treatment of monocytic cell lines with phorbol esters (16,22,23), which are strong NF-B activators, we assayed the effect of NF-B modulators on the PECAM-1 cell-surface expression and gene promoter activity. PDTC has been described as a potent inhibitor of NF-B activation (28).…”

Regulation of Endothelial Cell Barrier Function by Antibody-driven Affinity Modulation of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1)

“…Issues like phosphorylation of the cytoplasmic domain (45) and the potential role of carbohydrate chains in homophilic binding (46) can now be explored at a molecular level using isolated, soluble forms of full-length PECAM-1. Finally, previous studies have revealed lineage-specific differences in the apparent molecular mass of PECAM-1 in differentiated leukemic cell lines, in endothelial cells, and in leukocyte populations (47). Whether such variations translate into differing adhesive properties can now readily be evaluated using nanodisc technology.…”

Platelet-Mimicry of Cancer Cells: Epiphenomenon with Clinical Significance

“…On the other hand, in CD31+ cells it is involved in the positive regulation of integrin functions. Ectopic expression of CD31 was found in lymphoma and leukemia cells [45] and also in various human cancer cell lines [46]. Similar to αIIbβ3, the ‘ectopic’ CD31 on tumor cells is functional, and is thought to be involved in tumor cell-endothelial cell interactions [46], or perhaps in vascular mimicry.…”