Renata Fleming, MD, PhD

Pronouns

She/Her/Hers

Rank

Research Fellow

Institution

MGH

BWH-MGH Title

Research Fellow

Department

Neurology

Authors

Renata Fleming; Bakhos Tannous

Characterization of Neuropeptide Profile in Glioblastoma Cancer Stem Cells: Are Neuropeptide a Key Factor for Resistance?

WMSS 2022

I have always been interested in the role of neuropeptides in central nervous system plasticity, for the last 5 years I have specifically focused on the contribution of neuropeptides in glioblastoma plasticity and resistance. As a research fellow at MGH under Dr. Bakhos Tannous’s guidance I have had the opportunity to experience an environment of respect and appreciation, where I could take part in high science projects and have my voice heard. I believe that sharing my work in the symposium would be a great chance to emphasize women’s achievements and MGH community support.

Background

Glioblastoma (GBM) is the most common and aggressive type of malignant brain tumor in adults. Despite multimodal treatment tumor tend to recur due to a subpopulation of stem-like cells (GSCs) also responsible for therapeutic resistance. GBM grows in a rich neurochemical milieu, but the impact of neurochemicals on gliomagenesis is largely unexplored. Neuropeptides are a group of signaling messengers that have been recognized as potent cellular growth factors for many cell types, including cancer. We hypothesized that neuropeptides could be involved in GSCs intercellular communication and therapeutic resistance.

Methods

We characterized for the first time the neuropeptide profile in different GBM molecular subtypes and investigated their role in GSCs therapeutic resistance. Gene expression analysis from pro-neural (PN, better prognosis) and mesenchymal (MES, worse prognosis) GSCs was performed based on the data from a custom RNA array for human neuropeptides.

Results

We found a differentially expressed neuropeptide profile in the different GSCs subtypes. VGF in particular was upregulated in MES compared to the PN subtype. Knockdown of VGF decreased GSCs proliferation and sensitized them to temozolomide therapy.

Conclusions

Neuropeptides could be one of the milieu factors linked to GBM plasticity and provide a new target for adjuvant therapy