Dataset Information

The expression of BST2 in human and experimental mouse brain tumors.

ABSTRACT: Glioblastoma multiforme (grade IV astrocytoma) is a highly malignant brain tumor with poor treatment options and an average lifespan of 15 months after diagnosis. Previous work has demonstrated that BST2 (bone marrow stromal cell antigen 2; also known as PDCA-1, CD137 and HM1.24) is expressed by multiple myeloma, endometrial cancer and primary lung cancer cells. BST2 is expressed on the plasma membrane, which makes it an ideal target for immunotherapy. Accordingly, several groups have shown BST2 mAb to be effective for targeting tumor cells. In this report, we hypothesized that BST2 is expressed in human and mouse brain tumors and plays a critical role in brain tumor progression. We show that BST2 expression is upregulated at both the mRNA and protein level in high grade when compared to low grade human astrocytoma (p<0.05). To test the relevance of BST2, we utilized the intracranially (IC)-injected GL261 cell-based malignant brain tumor mouse model. We show that BST2 mRNA expression is increased in mouse brain IC-injected with GL261 cells, when compared to mouse brain IC-injected with saline at 3 weeks post-operative (p<0.05). Furthermore, BST2 immunofluorescence predominantly localized to mouse brain tumor cells. Finally, mice IC-injected with GL261 cells transduced with shRNA for BST2±preincubated with BST2 mAb show no difference in overall lifespan when compared to mice IC-injected with GL261 cells transduced with a scrambled shRNA±preincubated with BST2 mAb. Collectively, these data show that while BST2 expression increases during brain tumor progression in both human and mouse brain tumors, it has no apparent consequences to overall lifespan in an orthotopic mouse brain tumor model.

SUBMITTER: Wainwright DA

PROVIDER: S-EPMC3139740 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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The expression of BST2 in human and experimental mouse brain tumors.

Wainwright Derek A DA Balyasnikova Irina V IV Han Yu Y Lesniak Maciej S MS

Experimental and molecular pathology 20110501 1

Glioblastoma multiforme (grade IV astrocytoma) is a highly malignant brain tumor with poor treatment options and an average lifespan of 15 months after diagnosis. Previous work has demonstrated that BST2 (bone marrow stromal cell antigen 2; also known as PDCA-1, CD137 and HM1.24) is expressed by multiple myeloma, endometrial cancer and primary lung cancer cells. BST2 is expressed on the plasma membrane, which makes it an ideal target for immunotherapy. Accordingly, several groups have shown BST2 ...[more]

PMID: 21565182

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Project description:AimExperimental animals, such as non-human primates (NHPs), mice, Zebrafish, and Drosophila, are frequently employed as models to gain insights into human physiology and pathology. In developmental neuroscience and related research fields, information about the similarities of developmental gene expression patterns between animal models and humans is vital to choose what animal models to employ. Here, we aimed to statistically compare the similarities of developmental changes of gene expression patterns in the brains of humans with those of animal models frequently used in the neuroscience field.MethodsThe developmental gene expression datasets that we analyzed consist of the fold-changes and P values of gene expression in the brains of animals of various ages compared with those of the youngest postnatal animals available in the dataset. By employing the running Fisher algorithm in a bioinformatics platform, BaseSpace, we assessed similarities between the developmental changes of gene expression patterns in the human (Homo sapiens) hippocampus with those in the dentate gyrus (DG) of the rhesus monkey (Macaca mulatta), the DG of the mouse (Mus musculus), the whole brain of Zebrafish (Danio rerio), and the whole brain of Drosophila (D. melanogaster).ResultsAmong all possible comparisons of different ages and animals in developmental changes in gene expression patterns within the datasets, those between rhesus monkeys and mice were highly similar to those of humans with significant overlap P-value as assessed by the running Fisher algorithm. There was the highest degree of gene expression similarity between 40-59-year-old humans and 6-12-year-old rhesus monkeys (overlap P-value = 2.1 × 10- 72). The gene expression similarity between 20-39-year-old humans and 29-day-old mice was also significant (overlap P = 1.1 × 10- 44). Moreover, there was a similarity in developmental changes of gene expression patterns between 1-2-year-old Zebrafish and 40-59-year-old humans (Overlap P-value = 1.4 × 10- 6). The overlap P-value of developmental gene expression patterns between Drosophila and humans failed to reach significance (30 days Drosophila and 6-11-year-old humans; overlap P-value = 0.0614).ConclusionsThese results indicate that the developmental gene expression changes in the brains of the rhesus monkey, mouse, and Zebrafish recapitulate, to a certain degree, those in humans. Our findings support the idea that these animal models are a valid tool for investigating the development of the brain in neurophysiological and neuropsychiatric studies.

Project description:Many neurodegenerative diseases have a hallmark regional and cellular pathology. Gene expression analysis of healthy tissues may provide clues to the differences that distinguish resistant and sensitive tissues and cell types. Comparative analysis of gene expression in healthy mouse and human brain provides a framework to explore the ability of mice to model diseases of the human brain. It may also aid in understanding brain evolution and the basis for higher order cognitive abilities. Here we compare gene expression profiles of human motor cortex, caudate nucleus, and cerebellum to one another and identify genes that are more highly expressed in one region relative to another. We separately perform identical analysis on corresponding brain regions from mice. Within each species, we find that the different brain regions have distinctly different expression profiles. Contrasting between the two species shows that regionally enriched genes in one species are generally regionally enriched genes in the other species. Thus, even when considering thousands of genes, the expression ratios in two regions from one species are significantly correlated with expression ratios in the other species. Finally, genes whose expression is higher in one area of the brain relative to the other areas, in other words genes with patterned expression, tend to have greater conservation of nucleotide sequence than more widely expressed genes. Together these observations suggest that region-specific genes have been conserved in the mammalian brain at both the sequence and gene expression levels. Given the general similarity between patterns of gene expression in healthy human and mouse brains, we believe it is reasonable to expect a high degree of concordance between microarray phenotypes of human neurodegenerative diseases and their mouse models. Finally, these data on very divergent species provide context for studies in more closely related species that address questions such as the origins of cognitive differences.

Dataset Information

The expression of BST2 in human and experimental mouse brain tumors.

Publications

The expression of BST2 in human and experimental mouse brain tumors.

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