Drug targets for Cancer: CD38

Drug Targets for Cancer: CD38 and Cancer

A role of CD38 in microglial function was also shown in vivo in a head trauma model where CD38 deficiency reduced the accumulation of activated MM in the injured brain area and worsened the recovery of the mice from the trauma. CD38 is a nicotinamide adenine dinucleotide (NAD) glycohydrolase and ADP-ribosyl cyclase. It is expressed by various cell types, including myeloid-derived cells. The extracellular enzymatic domain of CD38 uses NAD+ and NADP+ to catalyze the formation of the calcium-mobilizing metabolites adenosine diphosphate ribose (ADPR), cyclic ADPR, and nicotinic acid adenine dinucleotide phosphate. Notably, CD38 may also act as a cell-surface receptor. CD38 can play a role in several biological systems, as indicated by studies using CD38-deficient mice. Accordingly, CD38 deficiency may impair both innate and adaptive immune responses. These include impaired neutrophile, monocyte, and dendritic cell trafficking and impaired T cell priming, as well as reduced humoral responses and enhanced susceptibility to infection. Additional effects associated with CD38 deficiency include attenuation of airway hyperreactivity and impairments of insulin secretion, osteoclast-mediated bone resorption,16 and oxytocin secretion. In cells of the immune system, levels of CD38 expression may vary as functions of the activation state, in a manner that is cell-type dependent. In T cells and in cells of the myeloid lineage, for example, the levels of expression increase upon activation. The expression of CD38 is also relevant in neoplastic cells. Specifically, in chronic lymphocytic leukemia, a high percentage of CD38-expressing leukemic cells is associated with unfavorable prognosis, as well as with cell activation and proliferation.

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Drug Targets for Cancer: CD38 Related Reference

Levy A, Blacher E, Vaknine H, Lund FE, Stein R, Mayo L. CD38 deficiency in the tumor microenvironment attenuates glioma progression and modulates features of tumor-associated microglia/macrophages. Neuro-Oncology. 2012;14(8):1037-1049.

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