Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement

Loan Bui; Alissa Hendricks; Jamie Wright; Cheng Jen Chuong; Digant Davé; Robert Bachoo; Young Tae Kim

doi:10.1038/srep26134

Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement

Loan Bui, Alissa Hendricks, Jamie Wright, Cheng Jen Chuong, Digant Davé, Robert Bachoo, Young Tae Kim

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Article number	26134
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep26134
State	Published - May 17 2016

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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.",

author = "Loan Bui and Alissa Hendricks and Jamie Wright and Chuong, {Cheng Jen} and Digant Dav{\'e} and Robert Bachoo and Kim, {Young Tae}",

note = "Funding Information: The authors are grateful for the support obtained from the Cancer Prevention and Research Institute of Texas (CPRIT, RP110041 and RP150711) and Office of President and Provost, The University of Texas at Arlington. The authors thank Drs. Yuxiao Sun, Tomoyuki Mashimo, and Suraj Nannepaga for technical assistance toward this work.",

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doi = "10.1038/srep26134",

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AU - Bui, Loan

AU - Hendricks, Alissa

AU - Wright, Jamie

AU - Chuong, Cheng Jen

AU - Davé, Digant

AU - Bachoo, Robert

AU - Kim, Young Tae

N1 - Funding Information: The authors are grateful for the support obtained from the Cancer Prevention and Research Institute of Texas (CPRIT, RP110041 and RP150711) and Office of President and Provost, The University of Texas at Arlington. The authors thank Drs. Yuxiao Sun, Tomoyuki Mashimo, and Suraj Nannepaga for technical assistance toward this work.

PY - 2016/5/17

Y1 - 2016/5/17

N2 - 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.

AB - 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.

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Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement

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