Glioblastoma multiforme (GBM), the most common and devastating intracranial malignant tumor accounts for 20% of all primary brain tumors and has a median survival rate of only 14 months. Cancer cells often disseminate far from primary tumors and individual glioma cells migrate from the gross tumor into the surrounding parenchyma, making complete surgical resection nearly impossible. This migratory capacity of malignant gliomas represents the greatest challenge to any potential therapy in spite of advances in surgery, chemotherapy and radiotherapy and growth of the remaining invasive cells leads to a recurrence incidence of 99%. What exactly regulates the migratory capacity of brain tumor cells is not fully understood and need to be studied. The main goal of this proposal is to understand the link between known pro- migratory signals such as epidermal growth factor (EGF) and Slit proteins with cell volume regulation. EGF and Slit proteins may play an important role in the modulation of invasive and migratory ability of GBM derived stem cells through Akt pathway that in turn regulates the activation of ion cotransport NKCC1. We propose to study invasive patterns and cell volume changes resulting in the extension of a leading process of a migrating cell, using various cell migration assays and measuring intracellular anion concentration. The results obtained from this work will help us understand the downstream signaling pathways involved in the activation of cascade mechanism responsible for brain tumor cell migration. Further, such knowledge will undoubtedly result in better therapeutic alternatives to current sub-optimal treatments for this devastating disease.
Glioblastoma multiforme (GBM) is the most common and devastating primary malignant tumor. Our project aims to study the migration of GBM-derived Brain Tumor Stem Cells (BTSCs). BTSCs are thought to be responsible for maintaining the bulk of the tumor and to induce recurrence after surgical resection, nevertheless the molecular mechanisms that regulate their migration are not known. In this study, we propose to understand the role of pro-migratory signals in brain tumor invasion in order to increase the available targets to prevent brain tumor dispersal.
|Mathioudakis, Nestoras; Sundaresh, Ram; Larsen, Alexandra et al. (2015) Expression of the pituitary stem/progenitor marker GFR?2 in human pituitary adenomas and normal pituitary. Pituitary 18:31-41|
|Abbadi, Sara; Rodarte, Julio J; Abutaleb, Ameer et al. (2014) Glucose-6-phosphatase is a key metabolic regulator of glioblastoma invasion. Mol Cancer Res 12:1547-59|
|Levy, Amanda F; Zayats, Maya; Guerrero-Cazares, Hugo et al. (2014) Influence of basement membrane proteins and endothelial cell-derived factors on the morphology of human fetal-derived astrocytes in 2D. PLoS One 9:e92165|
|Capilla-Gonzalez, Vivian; Guerrero-Cazares, Hugo; Bonsu, Janice M et al. (2014) The subventricular zone is able to respond to a demyelinating lesion after localized radiation. Stem Cells 32:59-69|
|Campos-Ordoñez, Tania; Herranz-Pérez, Vicente; Chaichana, Kaisorn L et al. (2014) Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone. Exp Neurol 261:236-44|
|Capilla-Gonzalez, Vivian; Cebrian-Silla, Arantxa; Guerrero-Cazares, Hugo et al. (2014) Age-related changes in astrocytic and ependymal cells of the subventricular zone. Glia 62:790-803|
|Chaichana, Kaisorn L; Jusue-Torres, Ignacio; Navarro-Ramirez, Rodrigo et al. (2014) Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol 16:113-22|
|Li, Qian; Wijesekera, Olindi; Salas, Sussan J et al. (2014) Mesenchymal stem cells from human fat engineered to secrete BMP4 are nononcogenic, suppress brain cancer, and prolong survival. Clin Cancer Res 20:2375-87|
|Tilghman, Jessica; Wu, Hao; Sang, Yingying et al. (2014) HMMR maintains the stemness and tumorigenicity of glioblastoma stem-like cells. Cancer Res 74:3168-79|
|Kundu, Arnab; Micholt, Liesbeth; Friedrich, Sarah et al. (2013) Superimposed topographic and chemical cues synergistically guide neurite outgrowth. Lab Chip 13:3070-81|
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