Glioblastoma (GBM) is the most common, aggressive and proliferative primary brain tumor in adults despite current therapeutic strategies that combine surgery, radio, and chemotherapy. The high invasive capacity of GBM makes total surgical resection virtually impossible, resulting in an extremely high recurrence rate. The ability to form a new tumor resides in a subpopulation of cells within the GBM called brain tumor initiating cells (BTICs). BTICs are undifferentiated cells with self-renewing and pluripotential capacity, with the added ability of forming tumors in vivo. Our group and others have reported that among primary GBMs, those located in close proximity to the lateral ventricles (LV) present multiple distinct features, including increased recurrence at distant locations, which negatively affect patients' survival. The cause for worse outcomes in patients suffering LV-proximal GBMs is not known. Possible explanations may involve the proximity of these tumors to the cerebrospinal fluid (CSF) and neurogenic niche in the sub-ventricular zone (SVZ). In a pilot study, we have determined that human non-cancer CSF repels BTICs migration in vitro. The molecules in the CSF responsible for this effect are not known. Here we propose to study the interactions between BTICs and different fractions of CSF. We hypothesize that CSF can induce a more aggressive behavior of GBM cells. We will perform this research using intraoperative human tissue. Upon completion of this study we will have gained a better understanding of the effects of CSF on GBM cells and will have discovered possible factors within CSF which influence BTICs and cancer progression. Ultimately, we hope to reveal specific targets for therapeutic intervention leading to increased survival in patients with GBM.

Public Health Relevance

GlioblastomaMultiforme(GBM)isthemostcommonandaggressivetumorinthebrain.AmongGBMs, thosethatarelocatednearthecerebrospinalfluid(CSF)aretheoneswiththeworstprognosis.Herewe willinvestigatetheeffectsofhumanCSFonhumanGBMcellsinvitroaninvivo.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21CA199295-01A1S1
Application #
9544413
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Soyombo-Shoola, Abigail Adebisi
Project Start
2016-09-15
Project End
2018-08-31
Budget Start
2016-09-15
Budget End
2017-08-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Mayo Clinic Jacksonville
Department
Type
DUNS #
153223151
City
Jacksonville
State
FL
Country
United States
Zip Code
32224
Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda et al. (2017) Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development. Stem Cells 35:1860-1865
Huang, Yu-Ja; Schiapparelli, Paula; Kozielski, Kristen et al. (2017) Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells. J Cell Sci 130:2459-2467