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CD38 deficiency in the tumor microenvironment attenuates glioma progression and modulates features of tumor-associated microglia/macrophages.
- Source :
-
Neuro-oncology [Neuro Oncol] 2012 Aug; Vol. 14 (8), pp. 1037-49. Date of Electronic Publication: 2012 Jun 14. - Publication Year :
- 2012
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Abstract
- Gliomas are the most frequent primary tumors of the brain, and for highly malignant gliomas there is no successful treatment. The tumor microenvironment contains large numbers of infiltrating microglia and macrophages (MM). There is increasing evidence that the tumor-associated MM support glioma expansion. CD38 is a multifunctional ectoenzyme that uses nicotinamide adenine dinucleotide as a substrate to generate second messengers. Previously we showed that CD38 deficiency modulates microglial "activation" and impaired recovery from head trauma by a microglia-associated mechanism. In view of the supportive role of MM in glioma progression and the role of CD38 in microglia activation, we hypothesize that deficiency of CD38 in the tumor microenvironment would inhibit glioma progression. Using the syngeneic GL261 model of glioma progression in wild-type and CD38 null mice, we show here that CD38 deficiency significantly attenuates glioma expansion and prolongs the life span of the glioma-bearing mice. The CD38 deficiency effect was associated with increased cell death and decreased metalloproteinase-12 expression in the tumor mass, as well as modulation of the tumor-induced MM properties, as indicated by a reduction in the expression of the MM marker F4/80 and matrix metalloproteinases. Our results thus suggest that CD38 participates in the tumor-supporting action of MM and that targeting CD38 might be a potential therapeutic approach for glioma treatment.
- Subjects :
- ADP-ribosyl Cyclase 1 deficiency
Animals
Brain Neoplasms immunology
Brain Neoplasms metabolism
Cell Separation
Disease Models, Animal
Disease Progression
Flow Cytometry
Glioma immunology
Glioma metabolism
Immunoblotting
Immunohistochemistry
Macrophages immunology
Male
Membrane Glycoproteins deficiency
Mice
Mice, Inbred C57BL
Mice, Knockout
Microglia immunology
Reverse Transcriptase Polymerase Chain Reaction
ADP-ribosyl Cyclase 1 metabolism
Brain Neoplasms pathology
Glioma pathology
Macrophages pathology
Membrane Glycoproteins metabolism
Microglia pathology
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-5866
- Volume :
- 14
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Neuro-oncology
- Publication Type :
- Academic Journal
- Accession number :
- 22700727
- Full Text :
- https://doi.org/10.1093/neuonc/nos121