Abstract Details

Title Investigating PINCH in Glioblastoma Multiforme: A Potential Adjuvant Therapy Target to Improve Treatment Outcomes

Topic Neuro-oncology

Presentation(s) P4 - Poster Session 4 (5:00 PM-6:00 PM)

Poster/Presentation
Number 6-012

Objective This study investigated the role of particularly-interesting-new-cysteine-histidine-rich protein-1 (PINCH1) in glioblastoma multiforme (GBM) progression and recurrence, as well as PINCH’s potential as a therapeutic target. The study focuses on understanding how changes in PINCH1 protein expression and post-translational modifications (PTM) impact cell cycle dynamics and cell survival upon chemotherapeutic agent exposure. Understanding PINCH1’s role in GBM development/progression may lead to improved treatment approaches.

Background Gliomas represent 80% of brain cancers, with glioblastoma multiforme (GBM) being the most common and aggressive type. Despite treatment, most low-grade astrocytomas progress to GBM, which has a nearly 100% recurrence rate within 9 months and a median survival of 15 months. GBM's invasiveness and resistance to therapy contribute to its poor prognosis.

Design/Methods Glioblastoma cell lines (U87, LN229, U251) and normal human primary astrocytes (HPA) were cultured in vitro under hypoxic and low-glucose conditions to mimic some aspects of the tumor microenvironment. PINCH1 expression was increased and decreased, and amino acids were mutated to regulate PTM in GBM cells lines and HPA. Cells were exposed to temozolomide (TMZ) and analyzed via immunolabeling with PINCH1, and glial fibrillary acidic protein (GFAP) antibodies followed by confocal microscopy. Flow cytometry assessed apoptosis and cell cycle changes in response to PINCH1 modulation under various stress conditions.

Results Preliminary findings indicated increased PINCH1 expression in cells subjected to stressors. GBM cells showed less cell death in the presence of stressors or TMZ. Of clinical relevance, PINCH1 overexpression decreased TMZ-induced apoptosis in GBM.

Conclusions Future studies will investigate how regulating PINCH1 increases GBM cell vulnerability to chemotherapy. We will explore the role of PINCH1 SUMOylation, a PTM that modulates chemotherapeutic resistance. We aim to assess the clinical feasibility of regulating PINCH1 as a strategy to enhance GBM cell sensitivity to treatment, prevent astrocytoma progression to GBM, and reduce recurrence rates.

Authors/Disclosures
Saikrishna Gaddam PRESENTER	Mr. Gaddam has nothing to disclose.
Iman Hasan	Miss Hasan has nothing to disclose.
Alvaro Garcia, PhD	Dr. Garcia has nothing to disclose.
T. Dianne Langford, PhD (Temple University)	T. Dianne Langford, PhD has nothing to disclose.

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