Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier
Breast cancer brain metastasis is a major clinical challenge and is associated with a dismal prognosis. Understanding the mechanisms underlying the early stages of brain metastasis can provide opportunities to develop efficient diagnostics and therapeutics for this significant clinical challenge. We...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/11/3851 |
| _version_ | 1797566707150094336 |
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| author | Golnaz Morad Cassandra C. Daisy Hasan H. Otu Towia A. Libermann Simon T. Dillon Marsha A. Moses |
| author_facet | Golnaz Morad Cassandra C. Daisy Hasan H. Otu Towia A. Libermann Simon T. Dillon Marsha A. Moses |
| author_sort | Golnaz Morad |
| collection | DOAJ |
| description | Breast cancer brain metastasis is a major clinical challenge and is associated with a dismal prognosis. Understanding the mechanisms underlying the early stages of brain metastasis can provide opportunities to develop efficient diagnostics and therapeutics for this significant clinical challenge. We have previously reported that breast cancer-derived extracellular vesicles (EVs) breach the blood–brain barrier (BBB) via transcytosis and can promote brain metastasis. Here, we elucidate the functional consequences of EV transport across the BBB. We demonstrate that brain metastasis-promoting EVs can be internalized by astrocytes and modulate the behavior of these cells to promote extracellular matrix remodeling in vivo. We have identified protein and miRNA signatures in these EVs that can lead to the interaction of EVs with astrocytes and, as such, have the potential to serve as targets for development of diagnostics and therapeutics for early detection and therapeutic intervention in breast cancer brain metastasis. |
| first_indexed | 2024-03-10T19:31:16Z |
| format | Article |
| id | doaj.art-0ce2038dc3da47d0ac3446bd384fe615 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:31:16Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0ce2038dc3da47d0ac3446bd384fe6152023-11-20T02:04:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012111385110.3390/ijms21113851Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain BarrierGolnaz Morad0Cassandra C. Daisy1Hasan H. Otu2Towia A. Libermann3Simon T. Dillon4Marsha A. Moses5Vascular Biology Program, Boston Children’s Hospital, Boston, MA 02115, USAVascular Biology Program, Boston Children’s Hospital, Boston, MA 02115, USADepartment of Electrical and Computer Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USABIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Beth Israel Deaconess Medical Center, Boston, MA 02115, USABIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center, Beth Israel Deaconess Medical Center, Boston, MA 02115, USAVascular Biology Program, Boston Children’s Hospital, Boston, MA 02115, USABreast cancer brain metastasis is a major clinical challenge and is associated with a dismal prognosis. Understanding the mechanisms underlying the early stages of brain metastasis can provide opportunities to develop efficient diagnostics and therapeutics for this significant clinical challenge. We have previously reported that breast cancer-derived extracellular vesicles (EVs) breach the blood–brain barrier (BBB) via transcytosis and can promote brain metastasis. Here, we elucidate the functional consequences of EV transport across the BBB. We demonstrate that brain metastasis-promoting EVs can be internalized by astrocytes and modulate the behavior of these cells to promote extracellular matrix remodeling in vivo. We have identified protein and miRNA signatures in these EVs that can lead to the interaction of EVs with astrocytes and, as such, have the potential to serve as targets for development of diagnostics and therapeutics for early detection and therapeutic intervention in breast cancer brain metastasis.https://www.mdpi.com/1422-0067/21/11/3851breast cancerbrain metastasisextracellular vesiclesmicroRNAblood–brain barrier |
| spellingShingle | Golnaz Morad Cassandra C. Daisy Hasan H. Otu Towia A. Libermann Simon T. Dillon Marsha A. Moses Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier International Journal of Molecular Sciences breast cancer brain metastasis extracellular vesicles microRNA blood–brain barrier |
| title | Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier |
| title_full | Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier |
| title_fullStr | Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier |
| title_full_unstemmed | Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier |
| title_short | Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier |
| title_sort | cdc42 dependent transfer of mir301 from breast cancer derived extracellular vesicles regulates the matrix modulating ability of astrocytes at the blood brain barrier |
| topic | breast cancer brain metastasis extracellular vesicles microRNA blood–brain barrier |
| url | https://www.mdpi.com/1422-0067/21/11/3851 |
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