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BSCI-15. METASTATIC BRAIN TUMOR TARGETING PEPTIDES ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS

To effectively target metastatic brain tumors (MBTs), the paradigm of treating MBTs after visualization on clinical imaging needs to be shifted to an understanding of the mechanisms that drive the formation and maintenance of brain metastasis-initiating cells (BMICs). Targeting this tumor sub-popula...

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Autores principales: Kim, JongMyung, Liu, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213402/
http://dx.doi.org/10.1093/noajnl/vdz014.013
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author Kim, JongMyung
Liu, James
author_facet Kim, JongMyung
Liu, James
author_sort Kim, JongMyung
collection PubMed
description To effectively target metastatic brain tumors (MBTs), the paradigm of treating MBTs after visualization on clinical imaging needs to be shifted to an understanding of the mechanisms that drive the formation and maintenance of brain metastasis-initiating cells (BMICs). Targeting this tumor sub-population, which may form as a result from activation of epithelial-mesenchymal transition, may allow for more effective means of isolating and targeting brain metastasis. In order to isolate BMICs, we have harvested cells from patient derived MBTs originating from lung cancer and cultured the cells using serum-free media conditions. In vivo phage display biopanning was used to isolate 12-amino acid length peptides that specifically target BMICs. Of the peptides recovered, one peptide, LBM4, was tested for specificity of binding to MBTs through in vitro and in vivo binding assays. When comparing patient derived metastatic brain tumors cells against brain metastasis cell lines, we found that both types of cells demonstrated similar morphology when grown in serum media conditions, but when grown in serum-free media, both demonstrated a tumor sphere morphology, similar to a stem cell-like state. LBM4 demonstrated specific binding to MBT cells over primary lung cancer cells in vitro through flow cytometry analysis and immunocytochemistry. Fluorescent tagged LBM4 intravenously injected into mice harboring intracranial BM demonstrated peptide localization to the tumor within the intracranial cavity visualized with live animal imaging. In vivo phage display biopanning is an effective tool that is able to isolate cell specific targeting peptides. MBT targeting peptides can potentially result in a shifting of the clinical treatment paradigm of brain metastases, through the development of more effective targeted therapeutics aimed at BMICs, as well as improving detection of MBT cells which may result in earlier tumor visualization as well as delineation of tumor recurrence versus radiation effects.
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spelling pubmed-72134022020-07-07 BSCI-15. METASTATIC BRAIN TUMOR TARGETING PEPTIDES ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS Kim, JongMyung Liu, James Neurooncol Adv Abstracts To effectively target metastatic brain tumors (MBTs), the paradigm of treating MBTs after visualization on clinical imaging needs to be shifted to an understanding of the mechanisms that drive the formation and maintenance of brain metastasis-initiating cells (BMICs). Targeting this tumor sub-population, which may form as a result from activation of epithelial-mesenchymal transition, may allow for more effective means of isolating and targeting brain metastasis. In order to isolate BMICs, we have harvested cells from patient derived MBTs originating from lung cancer and cultured the cells using serum-free media conditions. In vivo phage display biopanning was used to isolate 12-amino acid length peptides that specifically target BMICs. Of the peptides recovered, one peptide, LBM4, was tested for specificity of binding to MBTs through in vitro and in vivo binding assays. When comparing patient derived metastatic brain tumors cells against brain metastasis cell lines, we found that both types of cells demonstrated similar morphology when grown in serum media conditions, but when grown in serum-free media, both demonstrated a tumor sphere morphology, similar to a stem cell-like state. LBM4 demonstrated specific binding to MBT cells over primary lung cancer cells in vitro through flow cytometry analysis and immunocytochemistry. Fluorescent tagged LBM4 intravenously injected into mice harboring intracranial BM demonstrated peptide localization to the tumor within the intracranial cavity visualized with live animal imaging. In vivo phage display biopanning is an effective tool that is able to isolate cell specific targeting peptides. MBT targeting peptides can potentially result in a shifting of the clinical treatment paradigm of brain metastases, through the development of more effective targeted therapeutics aimed at BMICs, as well as improving detection of MBT cells which may result in earlier tumor visualization as well as delineation of tumor recurrence versus radiation effects. Oxford University Press 2019-08-12 /pmc/articles/PMC7213402/ http://dx.doi.org/10.1093/noajnl/vdz014.013 Text en © The Author(s) 2019. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Kim, JongMyung
Liu, James
BSCI-15. METASTATIC BRAIN TUMOR TARGETING PEPTIDES ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS
title BSCI-15. METASTATIC BRAIN TUMOR TARGETING PEPTIDES ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS
title_full BSCI-15. METASTATIC BRAIN TUMOR TARGETING PEPTIDES ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS
title_fullStr BSCI-15. METASTATIC BRAIN TUMOR TARGETING PEPTIDES ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS
title_full_unstemmed BSCI-15. METASTATIC BRAIN TUMOR TARGETING PEPTIDES ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS
title_short BSCI-15. METASTATIC BRAIN TUMOR TARGETING PEPTIDES ISOLATED THROUGH PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS
title_sort bsci-15. metastatic brain tumor targeting peptides isolated through phage display biopanning against brain metastasis-initiating cells
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213402/
http://dx.doi.org/10.1093/noajnl/vdz014.013
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