The expression of BST2 in human and experimental mouse brain tumors

The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
Experimental and Molecular Pathology (Impact Factor: 2.88). 05/2011; 91(1):440-6. DOI: 10.1016/j.yexmp.2011.04.012
Source: PubMed

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.

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    • "BST-2 was first identified on plasma cells and stromal cells (Goto et al., 1994; Ishikawa et al., 1995). BST-2 expression has also been reported on several types of cancers including multiple myeloma (Goto et al., 1994; Tai et al., 2012; Wang et al., 2009) Bcell lymphoma (Schliemann et al., 2010), lung cancer (Wang et al., 2009), head and neck squamous cell carcinomas (Silveira et al., 2008), endometrial cancer (Yokoyama et al., 2012), brain cancer (Wainwright et al., 2011) and bone metastatic breast cancer (Cai et al., 2009). Although it is unclear what function BST-2 serves on transformed cells, it was found that expression on breast cancer cells results in increased migration and proliferation suggesting that it might promote metastasis (Cai et al., 2009). "
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    ABSTRACT: BST-2 (also known as tetherin, CD317, or HM1.24) was first described as a potent interferon-inducible host antiviral factor nearly five years ago. Since that time, numerous reports have been published regarding the antiviral activity and immunological properties of this protein. BST-2 blocks viral replication by inhibiting enveloped virus budding from the surface of infected cells. To counteract this, most viruses have developed strategies to antagonize BST-2, each employing a unique mechanism. In this review, we summarize the antiviral function, structural biology and immunobiology of BST-2. Taken together, our current understanding of BST-2 suggests potential avenues as well as challenges to exploiting its action in the development of broad spectrum antiviral treatments.
    Molecular Immunology 12/2012; 54(2):132-139. DOI:10.1016/j.molimm.2012.11.008 · 3.00 Impact Factor
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    • "BST-2 has two mainly bio-functions in cells: the first is that BST-2 is identified as a host cell 'restriction factor' counteracted the accessory protein Vpu of enveloped viruses on cell surface and then limits the spread of enveloped viruses (Evans et al., 2010); the second is that BST-2 is preferentially overexpressed on multiple myeloma cells and several cancer cells, and played a key role in tumor progression (Wang et al., 2009; Wainwright et al., 2011). It means that BST-2 is helpful for cell progression in several myeloma and cancer cells. "
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    ABSTRACT: MT1-MMP (membrane type 1-matrix metalloproteinase) plays important roles in cell growth and tumor invasion via mediating cleavage of MMP2/gelatinase A and a variety of substrates including type I collagen. BST-2 (bone marrow stromal cell antigen 2) is a membrane tetherin whose expression dramatically reduces the release of a broad range of enveloped viruses including HIV from infected cells. In this study, we provided evidence that both transient and IFN-α induced BST-2 could decrease the activity of MMP2 via binding to cellular MT1-MMP on its C-terminus and inhibiting its proteolytic activity; and finally block cell growth and migration. Zymography gel and Western blot experiments demonstrated that BST-2 decreased MMP2 activity, but no effect on the expression of MMP2 and MT1-MMP genes. Confocal and immunoprecipitation data showed that BST-2 co-localized and interacted with MT1-MMP. This interaction inhibited the proteolytic enzyme activity of MT1-MMP, and blocked the activation of proMMP2. Experimental results of C-terminus deletion mutant of MT1-MMP showed that activity of MMP2 was no change and also no interaction existed between the mutant and BST-2 after co-transfection with the mutant and BST-2. It meant that C-terminus of MT1-MMP played a key role in the interaction with BST-2. In addition, cell growth in 3D type I collagen gel lattice and cell migration were all inhibited by BST-2. Taken together, BST-2, as a membrane protein and a tetherin of enveloped viruses, was a novel inhibitor of MT1-MMP and could be considerable as an inhibitor of cancer cell growth and migration on clinic.
    Journal of Cellular Biochemistry 03/2012; 113(3):1013-21. DOI:10.1002/jcb.23433 · 3.37 Impact Factor
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    Journal of leukocyte biology 11/2012; 93(3). DOI:10.1189/jlb.0812397 · 4.99 Impact Factor
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