title: Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement.
abstract: Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII), and genetically modified mouse astrocytes (wild type, p53-/-, p53-/- PTEN-/-, p53-/- Braf, and p53-/- PTEN-/- Braf). We found that loss of PTEN combined with Braf activation resulted in higher viability in narrow microchannels. In addition, Braf conferred increased resistance to the microtubule-stabilizing drug Taxol in narrow confinement. Similarly, survival of D54-EGFRvIII cells was unaffected following treatment with Taxol, whereas the viability of D54 cells was reduced by 75% under these conditions. Taken together, our data suggests key targets for anticancer drugs based on cellular genotypes and their specific survival phenotypes during confined migration.
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, TX, USA.
authors.forename: Loan
authors.initials: L
authors.lastname: Bui
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, TX, USA.
authors.forename: Alissa
authors.initials: A
authors.lastname: Hendricks
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, TX, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Wright
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, TX, USA.
authors.forename: Cheng-Jen
authors.initials: CJ
authors.lastname: Chuong
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, TX, USA.|Advanced Imaging Research Center, UT Southwestern Medical Center, TX, USA.
authors.forename: Digant
authors.initials: D
authors.lastname: Davé
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, TX, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bachoo
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, TX, USA.|Department of Urology, UT Southwestern Medical Center, TX, USA.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Kim
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000172:deficiency / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017239:Paclitaxel