title: Di-ethylhexylphthalate (DEHP) modulates cell invasion, migration and anchorage independent growth through targeting S100P in LN-229 glioblastoma cells.
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.
authors.affiliation: Laboratory of Cancer Immunology Target Identification and Validation, Department of Biology, College of Science, Engineering and Technology, Jackson State University, 1400 J. R. Lynch Street, Jackson, MS 39217, USA. jennifer.n.sims@students.jsums.edu.
authors.forename: Jennifer Nicole
authors.initials: JN
authors.lastname: Sims
authors.affiliation: Laboratory of Cancer Immunology Target Identification and Validation, Department of Biology, College of Science, Engineering and Technology, Jackson State University, 1400 J. R. Lynch Street, Jackson, MS 39217, USA. barbara.e.graham@jsums.edu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Graham
authors.affiliation: College of Science, Engineering and Technology, Jackson State University, 1400 J. R. Lynch Street, Jackson, MS 39217, USA. maricica.pacurari@jsums.edu.
authors.forename: Maricica
authors.initials: M
authors.lastname: Pacurari
authors.affiliation: Department of Behavioral and Environmental Health, Jackson State University, 1400 J. R. Lynch Street, Jackson, MS 39217, USA. sophia.s.leggett@jsums.edu.
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Leggett
authors.affiliation: College of Science, Engineering and Technology, Jackson State University, 1400 J. R. Lynch Street, Jackson, MS 39217, USA. paul.b.tchounwou@jsums.edu.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Tchounwou
authors.affiliation: Laboratory of Cancer Immunology Target Identification and Validation, Department of Biology, College of Science, Engineering and Technology, Jackson State University, 1400 J. R. Lynch Street, Jackson, MS 39217, USA. kenneth.ndebele@jsums.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ndebele
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004785:Environmental Pollutants; D009363:Neoplasm Proteins; C103003:S100P protein, human; D004051:Diethylhexyl Phthalate