Abstract
Glioblastoma multiforme (GBM) is the most aggressive brain cancer with a median survival of 1–2 years. The treatment of GBM includes surgical resection, radiation and chemotherapy, which minimally extends survival. This poor prognosis necessitates the identification of novel molecular targets associated with glioblastoma. S100P is associated with drug resistance, metastasis, and poor clinical outcomes in many malignancies. The functional role of S100P in glioblastoma has not been fully investigated. In this study, we examined the role of S100P mediating the effects of the environmental contaminant, DEHP, in glioblastoma cells (LN-229) by assessing cell proliferation, apoptosis, anchorage independent growth, cell migration and invasion following DEHP exposure. Silencing S100P and DEHP treatment inhibited LN-229 glioblastoma cell proliferation and induced apoptosis. Anchorage independent growth study revealed significantly decreased colony formation in shS100P cells. We also observed reduced cell migration in cells treated with DEHP following S100P knockdown. Similar results were observed in spheroid formation and expansion. This study is the first to demonstrate the effects of DEHP on glioblastoma cells, and implicates S100P as a potential therapeutic target that may be useful as a drug response biomarker.
Highlights
Glioblastoma multiforme (GBM) is the most common and most malignant human brain tumor, with an incidence of 4 out of 100,000 per year [1]
The protein expression diminished to nearly non-detectable levels in the LN-229 cells infected with shS100P, compared with those infected with the control shGFP or uninfected LN-229 cells and no changes in β-actin expression were observed
We observed similar patterns and levels of inhibition in 3 other glioblastoma cell lines suggesting that S100P plays a major role in proliferation of glioblastoma cells
Summary
Glioblastoma multiforme (GBM) is the most common and most malignant human brain tumor, with an incidence of 4 out of 100,000 per year [1]. GBM is extremely invasive and difficult to treat surgically. It is distinguished by severe and aberrant vascularization and high resistance to radiotherapy (RT) and chemotherapy [1,2]. There are no known risk factors directly related to GBM. Long-term exposure to various carcinogens, including heavy metals and aromatic chemicals has been associated with an increased risk for GBM [4]. Exposure to these environmental chemicals can either stimulate cell proliferation or lead to cell death, impacting tumor growth [5]. Phthalates are a group of industrial chemicals that are used as plasticizers, solvents, lubricants, fixatives, and as detergents in personal care products [6]
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