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Updated: Mar 15, 2026
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
The complex role of transglutaminase 2 in glioblastoma proliferation
Soner Gundemir1, Alina Monteagudo1, Abdullah Akbar1
1Department of Anesthesiology, University of Rochester, Rochester, New York; Department of Pharmacology and Physiology, University of Rochester, Rochester, New York; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada.
Background:
Glioblastomas (GBMs) are a heterogeneous group of primary brain tumors. These tumors are resistant to therapeutic interventions and invariably recur after surgical resection. The multifunctional protein transglutaminase 2 (TG2) has been shown to promote cell survival in a number of different tumors. There is also evidence that TG2 may be a pro-survival factor in GBMs. However, the roles that TG2 plays in facilitating GBM survival and proliferation have not yet been clearly delineated .
Methods:
The functions of TG2 are often cell- and context-specific. Therefore, in this study we examined the ability of TG2 to facilitate GBM proliferation using colony formation assays and 5-ethynyl-2'-deoxyuridine (EdU) incorporation in several different GBM cell lines as well as neurospheres derived from patient tumors representing the 3 major subtypes of GBM tumors (mesenchymal, proneural, and classical) and maintained in the absence of serum. TG2 knockdown or selective TG2 inhibitors were used to modulate TG2 expression and activity.
Results:
We show that TG2 plays differential roles in the proliferative process depending on the cell type. In most, but not all, GBM models TG2 plays a crucial role in the proliferative process, and some but not all TG2 inhibitors were highly effective at reducing proliferation in a large subset of the GBM models.
Conclusion:
Our results show that TG2 plays an important-but notoriously context-specific-role in GBM cell biology. Nonetheless, as future studies unravel the genetic "fingerprints" that make TG2 inhibitors effective, this information could be exploited to develop TG2 inhibitors into personalized GBM therapies.
Insights
Transglutaminase 2 (TG2) plays a context-specific role in glioblastoma (GBM) proliferation. Targeting TG2 shows promise for personalized GBM therapies, though effectiveness varies by GBM subtype.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Molecular Therapeutics
Background:
- Glioblastomas (GBMs) are aggressive primary brain tumors known for therapeutic resistance and recurrence post-surgery.
- The multifunctional protein transglutaminase 2 (TG2) is implicated in cancer cell survival, with potential roles in GBMs that require further delineation.
Purpose of the Study:
- To investigate the specific roles of TG2 in facilitating glioblastoma (GBM) cell proliferation and survival.
- To assess the efficacy of TG2 modulation (knockdown or inhibition) on GBM growth across different tumor subtypes.
Main Methods:
- Utilized colony formation assays and 5-ethynyl-2'-deoxyuridine (EdU) incorporation to measure GBM proliferation.
- Examined TG2's function in diverse GBM cell lines and patient-derived neurospheres representing mesenchymal, proneural, and classical subtypes.
- Employed TG2 knockdown and selective TG2 inhibitors to modulate TG2 activity.
Main Results:
- TG2 demonstrated differential roles in GBM proliferation, contingent upon cell type and context.
- TG2 was found to be crucial for proliferation in most GBM models studied.
- Selective TG2 inhibitors showed significant efficacy in reducing proliferation in a substantial subset of GBM models.
Conclusions:
- TG2 plays a significant, yet context-specific, role in glioblastoma cell biology.
- Understanding the genetic factors influencing TG2 inhibitor efficacy is key to developing personalized GBM therapies.
