NAD(+)-metabolizing ecto-enzymes shape tumor-host interactions

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BlankNAD(+)-metabolizing ecto-enzymes shape tumor-host interactions: The chronic

lymphocytic leukemia model.

T Vaisitti, V Audrito, S Serra, C Bologna, D Brusa, F Malavasi, and S Deaglio

FEBS Lett, April 20, 2011; .

Department of Genetics, Biology and Biochemistry, University of Turin, 10126

Turin, Italy; Human Genetics Foundation (HuGeF), 10126 Turin, Italy.

Nicotinamide adenine dinucleotide (NAD(+)) is an essential co-enzyme that can be

released in the extracellular milieu. Here, it may elicit signals through

binding purinergic receptors. Alternatively, NAD(+) may be dismantled to

adenosine, up-taken by cells and transformed to reconstitute the intracellular

nucleotide pool. An articulated ecto-enzyme network is responsible for the

nucleotide-nucleoside conversion. CD38 is the main mammalian enzyme that

hydrolyzes NAD(+), generating Ca(2+)-active metabolites. Evidence suggests that

this extracellular network may be altered or used by tumor cells to (i) nestle

in protected areas, and (ii) evade the immune response. We have exploited

chronic lymphocytic leukemia as a model to test the role of the ecto-enzyme

network, starting by analyzing the individual elements that make up the whole

picture.

PMID: 21514298