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Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors
Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196187/ https://www.ncbi.nlm.nih.gov/pubmed/25051370 |
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author | Blanco, Víctor M. Chu, Zhengtao Vallabhapurapu, Subrahmanya D. Sulaiman, Mahaboob K. Kendler, Ady Rixe, Olivier Warnick, Ronald E. Franco, Robert S. Qi, Xiaoyang |
author_facet | Blanco, Víctor M. Chu, Zhengtao Vallabhapurapu, Subrahmanya D. Sulaiman, Mahaboob K. Kendler, Ady Rixe, Olivier Warnick, Ronald E. Franco, Robert S. Qi, Xiaoyang |
author_sort | Blanco, Víctor M. |
collection | PubMed |
description | Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. In this study, we first characterize SapC-DOPS bioavailability and antitumor effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity towards phosphatidylserine by showing that glioblastoma targeting is abrogated after in vivo exposure to lactadherin, which binds phosphatidylserine with high affinity. Second, we demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in vivo, in mouse models of brain metastases derived from human breast or lung cancer cells. Third, we demonstrate that SapC-DOPS nanovesicles have cytotoxic activity against metastatic breast cancer cells in vitro, and prolong the survival of mice harboring brain metastases. Taken together, these results support the potential of SapC-DOPS for the diagnosis and therapy of primary and metastatic brain tumors. |
format | Online Article Text |
id | pubmed-4196187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-41961872014-10-21 Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors Blanco, Víctor M. Chu, Zhengtao Vallabhapurapu, Subrahmanya D. Sulaiman, Mahaboob K. Kendler, Ady Rixe, Olivier Warnick, Ronald E. Franco, Robert S. Qi, Xiaoyang Oncotarget Research Paper Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. In this study, we first characterize SapC-DOPS bioavailability and antitumor effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity towards phosphatidylserine by showing that glioblastoma targeting is abrogated after in vivo exposure to lactadherin, which binds phosphatidylserine with high affinity. Second, we demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in vivo, in mouse models of brain metastases derived from human breast or lung cancer cells. Third, we demonstrate that SapC-DOPS nanovesicles have cytotoxic activity against metastatic breast cancer cells in vitro, and prolong the survival of mice harboring brain metastases. Taken together, these results support the potential of SapC-DOPS for the diagnosis and therapy of primary and metastatic brain tumors. Impact Journals LLC 2014-07-14 /pmc/articles/PMC4196187/ /pubmed/25051370 Text en Copyright: © 2014 Blanco et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Blanco, Víctor M. Chu, Zhengtao Vallabhapurapu, Subrahmanya D. Sulaiman, Mahaboob K. Kendler, Ady Rixe, Olivier Warnick, Ronald E. Franco, Robert S. Qi, Xiaoyang Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors |
title | Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors |
title_full | Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors |
title_fullStr | Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors |
title_full_unstemmed | Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors |
title_short | Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors |
title_sort | phosphatidylserine-selective targeting and anticancer effects of sapc-dops nanovesicles on brain tumors |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196187/ https://www.ncbi.nlm.nih.gov/pubmed/25051370 |
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