The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target
Open accessAbstract
Glioblastoma is highly enriched with macrophages, and osteopontin (OPN) expression levels correlate with glioma grade and the degree of macrophage infiltration; thus, we studied whether OPN plays a crucial role in immune modulation. Quantitative PCR, immunoblotting, and ELISA were used to determine OPN expression. Knockdown of OPN was achieved using complementary siRNA, shRNA, and CRISPR/Cas9 techniques, followed by a series of in vitro functional migration and immunological assays. OPN gene-deficient mice were used to examine the roles of non-tumor-derived OPN on survival of mice harboring intracranial gliomas. Patients with mesenchymal glioblastoma multiforme (GBM) show high OPN expression, a negative survival prognosticator. OPN is a potent chemokine for macrophages, and its blockade significantly impaired the ability of glioma cells to recruit macrophages. Integrin αvβ5 (ITGαvβ5) is highly expressed on glioblastoma-infiltrating macrophages and constitutes a major OPN receptor. OPN maintains the M2 macrophage gene signature and phenotype. Both tumor-derived and host-derived OPN were critical for glioma development. OPN deficiency in either innate immune or glioma cells resulted in a marked reduction in M2 macrophages and elevated T cell effector activity infiltrating the glioma. Furthermore, OPN deficiency in the glioma cells sensitized them to direct CD8+ T cell cytotoxicity. Systemic administration in mice of 4-1BB-OPN bispecific aptamers was efficacious, increasing median survival time by 68% (P < 0.05). OPN is thus an important chemokine for recruiting macrophages to glioblastoma, mediates crosstalk between tumor cells and the innate immune system, and has the potential to be exploited as a therapeutic target.
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Osteopontin: role in cell signaling and cancer progression
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Glioma cancer stem cells induce immunosuppressive macrophages/microglia
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Self-citationPietras, A., Katz, A. M., Ekström, E. J., Wee, B., Halliday, J. J., Pitter, K. L., Werbeck, J. L., Amankulor, N. M., Huse, J. T., & Holland, E. C. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.01.005 · Cited by 540
Self-citationGlioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype
Gabrusiewicz, K., Rodriguez, B., Wei, J., Hashimoto, Y., Healy, L. M., Maiti, S. N., Thomas, G., Zhou, S., Wang, Q., Elakkad, A., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.85841 · Cited by 445
Self-citationThe role of Osteopontin in tumor metastasis
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Self-citationYuan, Z., Li, Y., Zhang, S., Wang, X., Dou, H., Yu, X., Zhang, Z., Yang, S., & Xiao, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01744-8 · Cited by 977
Molecular Heterogeneity and Immunosuppressive Microenvironment in Glioblastoma
DeCordova, S., Shastri, A., Tsolaki, A. G., Yasmin, H., Klein, L., Singh, S. K., & Kishore, U. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01402 · Cited by 346
Symbiotic Macrophage-Glioma Cell Interactions Reveal Synthetic Lethality in PTEN-Null Glioma
Chen, P., Zhao, D., Li, J., Liang, X., Li, J., Chang, A., Henry, V. K., Lan, Z., Spring, D. J., Rao, G., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.05.003 · Cited by 339
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Metadata
- Authors
- Wei, J., Marisetty, A., Schrand, B., Gabrusiewicz, K., Hashimoto, Y., Ott, M., Grami, Z., Kong, L.-Y., Ling, X., Caruso, H., Zhou, S., Wang, Y. A., Fuller, G. N., Huse, J., Gilboa, E., Kang, N., Huang, X., Verhaak, R., Li, S., & Heimberger, A. B.
- Venue
- Journal of Clinical Investigation
- Published
- 2018-11-19
- Volume
- 129
- Issue
- 1
- Pages
- 137-149
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2896996016
- Cited by
- 396
- References
- 40
- FWCI
- 14.97
- Type
- journal article
- Language
- en
- Open access
- green
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- Wei, J., Marisetty, A., Schrand, B., Gabrusiewicz, K., Hashimoto, Y., Ott, M., Grami, Z., Kong, L.-Y., Ling, X., Caruso, H., Zhou, S., Wang, Y. A., Fuller, G. N., Huse, J., Gilboa, E., Kang, N., Huang, X., Verhaak, R., Li, S., & Heimberger, A. B. (2018). Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target. Journal of Clinical Investigation. https://doi.org/10.1172/jci121266
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