The expression of BST2 in human and experimental mouse brain tumors

Derek A. Wainwright, Irina V. Balyasnikova, Yu Han, Maciej S. Lesniak*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)440-446
Number of pages7
JournalExperimental and Molecular Pathology
Volume91
Issue number1
DOIs
StatePublished - Aug 1 2011

Fingerprint

Brain Neoplasms
Tumors
Brain
Glioblastoma
Cells
Small Interfering RNA
Lung Neoplasms
Messenger RNA
Astrocytoma
Endometrial Neoplasms
Multiple Myeloma
Mesenchymal Stromal Cells
Cell membranes
Immunotherapy
Fluorescent Antibody Technique
Bone
Cell Membrane
Antigens

Keywords

  • BST2
  • Bone marrow stromal cell antigen
  • CD137
  • Gene therapy
  • Glioblastoma
  • Glioma
  • HM1.24
  • Immunotherapy
  • PDCA-1

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

Cite this

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title = "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.",
keywords = "BST2, Bone marrow stromal cell antigen, CD137, Gene therapy, Glioblastoma, Glioma, HM1.24, Immunotherapy, PDCA-1",
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AU - Balyasnikova, Irina V.

AU - Han, Yu

AU - Lesniak, Maciej S.

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AB - 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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