Erythrocyte CD38 as a prognostic marker in cancer
Department of Biophysics, Istanbul Faculty of Medicine, Istanbul University, Capa-Istanbul, Turkey. Hematology (Amsterdam, Netherlands)
(Impact Factor: 1.25).
11/2007; 12(5):409-14. DOI: 10.1080/10245330701383841
Surface antigen CD38 which is a multifunctional protein with enzymatic and receptorial properties is involved in many processes of cell proliferation and activation. It is widely expressed within the hematopoetic system, and its expression is stimulated by proinflammatory cytokines. CD38-associated enzymatic activities in erythrocytes from cancer patients were investigated in this context.
Erythrocyte NAD glycohydrolase and ADP-ribosyl cyclase activities in normal individuals and cancer patients were compared and correlation of these activities to CEA values and anemia were determined. Changes in CD38-expression were followed by SDS-PAGE and Western blot analysis of erythrocyte membrane proteins.
Erythrocyte NAD glycohydrolase and ADP-ribosyl cyclase activities were significantly increased in cancer, in parallel to enhancement of CD38 expression and in correlation with CEA values and anemia.
An increased expression of CD38 which may be due to action of proinflammatory cytokines produced in tumor-host reactions appears to account for the elevations in erythrocyte CD38-associated enzyme activities in cancer patients. The changes in these enzyme activities may provide a prognostic outlook in view of their apparently close correlation to tumor progressions.
Available from: Ozlem Demir Coşkun
- "Cyclic ADP-ribose, the product of CD38 ADP-ribosyl cyclase activity, has received considerable interest as an inositol 1,4,5-triphosphate (IP-3)-independent Ca2+-mobilizer. Moreover, CD38 expression has gained importance as a prognostic marker in chronic lymphocytic leukemia (CLL) (4,5), HIV infection (6) and cancer (7,8). "
[Show abstract] [Hide abstract]
ABSTRACT: In the present study, NAD(+) glycohydrolase was purified from serum samples collected from healthy individuals using ammonium sulfate fractionation, Affi-Gel blue (Cibacron Blue F3GA) affinity chromatography, Sephadex G-100 column chromatography and isoelectric focusing. The final step was followed by a second Sephadex G-100 column chromatography assay in order to remove the ampholytes from the isoelectric focusing step. In terms of enhancement of specific activity, the NAD(+) glycohydrolase protein was purified ∼480-fold, with a yield of 1% compared with the initial serum fraction. The purified fraction appeared to be homogeneous, with a molecular weight of 39 kDa, as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, and also corresponded to the soluble (monomeric) form of surface antigen CD38.
Available from: cancerres.aacrjournals.org
[Show abstract] [Hide abstract]
ABSTRACT: Retinoic acid (RA) is known to regulate cell growth and differentiation. In HL-60 human myeloblastic leukemia cells, it causes mitogen-activated protein kinase (MAPK) signaling leading to myeloid differentiation and G(0) cell cycle arrest. This communication reports that expression of the Cbl adaptor caused enhanced extracellular signal-regulated kinase 2 activation and promoted RA-induced differentiation and G(0)-arrest. Stable transfectants ectopically expressing c-Cbl underwent myeloid differentiation faster than wild-type (wt) cells when treated with RA. In contrast, c-Cbl knockdown stable transfectants differentiated slower than wt cells when treated with RA. Cells ectopically expressing c-Cbl had enhanced CD38 expression when treated with RA, and cells ectopically expressing CD38 had enhanced c-Cbl expression, even without with RA, suggesting an interaction between c-Cbl and CD38. Fluorescence resource energy transfer and coimmunoprecipitation showed that c-Cbl and CD38 bind each other. RA causes the gradual down-regulation and eventual loss of c-Cbl expression, resulting in loss of the Cbl-CD38 interaction, suggesting that c-Cbl plays a relatively early role in promoting RA-induced differentiation. RA-induced differentiation can thus be propelled by c-Cbl and by CD38, both of which bind together, enhance the expression of each other, and cause MAPK signaling. There thus seems to be a cooperative role for c-Cbl and CD38, reflected in their direct binding, in propulsion of RA-induced differentiation.
Available from: Andrew Yen
[Show abstract] [Hide abstract]
ABSTRACT: Retinoic acid (RA) causes HL-60 human myeloblastic leukemia cell myeloid differentiation that is dependent on MAPK signaling. The process is propelled by c-Cbl, which binds the CD38 receptor as part of a signaling complex generating MAPK signaling. Here we report that the capability of c-Cbl to do this is lost in the G306E tyrosine kinase-binding domain mutant. Unlike wild-type (WT) c-Cbl, the G306E mutant c-Cbl fails to propel RA-induced differentiation, and disrupts the normal association with CD38. The G306E mutant does, like WT c-Cbl, co-immunoprecipitate with Vav, Slp-76, and p38. But unlike WT c-Cbl, does not cause MAPK signaling. In contrast, the C381A Ring finger domain mutant functions like WT c-Cbl. It binds CD38 and is part of the same apparent c-Cbl/Slp-76/Vav/p38 signaling complex. The C381A mutant causes MAPK signaling and propels RA-induced differentiation. In addition to HL-60 cells and their WT or mutant c-Cbl stable transfectants, the c-Cbl/Vav/Slp-76 complex is also found in NB4 cells where c-Cbl was previously also found to bind CD38. The data are consistent with a model in which the G306E mutant c-Cbl forms a signaling complex that includes Slp-76, Vav, and p38; but does not drive MAPK signaling because it fails to bind the CD38 receptor. Without the G306E mutation the c-Cbl unites CD38 with the signaling complex and delivers a MAPK signal that drives RA-induced differentiation. The results demonstrate the importance of the Gly306 residue in the ability of c-Cbl to propel RA-induced differentiation.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.