Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment
Ewing sarcoma (EwS) is a highly aggressive cancer and the second most common malignant bone tumor of children and young adults. Although patients with localized disease have a survival rate of approximately 75%, the prognosis for patients with metastatic disease remains dismal (<30%) and has...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.726205/full |
| _version_ | 1818573759555043328 |
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| author | Manideep C. Pachva Manideep C. Pachva Horton Lai Horton Lai Andy Jia Andy Jia Melanie Rouleau Melanie Rouleau Poul H. Sorensen Poul H. Sorensen |
| author_facet | Manideep C. Pachva Manideep C. Pachva Horton Lai Horton Lai Andy Jia Andy Jia Melanie Rouleau Melanie Rouleau Poul H. Sorensen Poul H. Sorensen |
| author_sort | Manideep C. Pachva |
| collection | DOAJ |
| description | Ewing sarcoma (EwS) is a highly aggressive cancer and the second most common malignant bone tumor of children and young adults. Although patients with localized disease have a survival rate of approximately 75%, the prognosis for patients with metastatic disease remains dismal (<30%) and has not improved in decades. Standard-of-care treatments include local therapies such as surgery and radiotherapy, in addition to poly-agent adjuvant chemotherapy, and are often associated with long-term disability and reduced quality of life. Novel targeted therapeutic strategies that are more efficacious and less toxic are therefore desperately needed, particularly for metastatic disease, given that the presence of metastasis remains the most powerful predictor of poor outcome in EwS. Intercellular communication within the tumor microenvironment is emerging as a crucial mechanism for cancer cells to establish immunosuppressive and cancer-permissive environments, potentially leading to metastasis. Altering this communication within the tumor microenvironment, thereby preventing the transfer of oncogenic signals and molecules, represents a highly promising therapeutic strategy. To achieve this, extracellular vesicles (EVs) offer a candidate mechanism as they are actively released by tumor cells and enriched with proteins and RNAs. EVs are membrane-bound particles released by normal and tumor cells, that play pivotal roles in intercellular communication, including cross-talk between tumor, stromal fibroblast, and immune cells in the local tumor microenvironment and systemic circulation. EwS EVs, including the smaller exosomes and larger microvesicles, have the potential to reprogram a diversity of cells in the tumor microenvironment, by transferring various biomolecules in a cell-specific manner. Insights into the various biomolecules packed in EwS EVs as cargos and the molecular changes they trigger in recipient cells of the tumor microenvironment will shed light on various potential targets for therapeutic intervention in EwS. This review details EwS EVs composition, their potential role in metastasis and in the reprogramming of various cells of the tumor microenvironment, and the potential for clinical intervention. |
| first_indexed | 2024-12-15T00:17:11Z |
| format | Article |
| id | doaj.art-ed72a8a1cae14ec283417b806cd8bd81 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-15T00:17:11Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ed72a8a1cae14ec283417b806cd8bd812022-12-21T22:42:26ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.726205726205Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor MicroenvironmentManideep C. Pachva0Manideep C. Pachva1Horton Lai2Horton Lai3Andy Jia4Andy Jia5Melanie Rouleau6Melanie Rouleau7Poul H. Sorensen8Poul H. Sorensen9Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaFaculty of Science, University of British Columbia, Vancouver, BC, CanadaDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaFaculty of Science, University of British Columbia, Vancouver, BC, CanadaDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaDepartment of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, CanadaEwing sarcoma (EwS) is a highly aggressive cancer and the second most common malignant bone tumor of children and young adults. Although patients with localized disease have a survival rate of approximately 75%, the prognosis for patients with metastatic disease remains dismal (<30%) and has not improved in decades. Standard-of-care treatments include local therapies such as surgery and radiotherapy, in addition to poly-agent adjuvant chemotherapy, and are often associated with long-term disability and reduced quality of life. Novel targeted therapeutic strategies that are more efficacious and less toxic are therefore desperately needed, particularly for metastatic disease, given that the presence of metastasis remains the most powerful predictor of poor outcome in EwS. Intercellular communication within the tumor microenvironment is emerging as a crucial mechanism for cancer cells to establish immunosuppressive and cancer-permissive environments, potentially leading to metastasis. Altering this communication within the tumor microenvironment, thereby preventing the transfer of oncogenic signals and molecules, represents a highly promising therapeutic strategy. To achieve this, extracellular vesicles (EVs) offer a candidate mechanism as they are actively released by tumor cells and enriched with proteins and RNAs. EVs are membrane-bound particles released by normal and tumor cells, that play pivotal roles in intercellular communication, including cross-talk between tumor, stromal fibroblast, and immune cells in the local tumor microenvironment and systemic circulation. EwS EVs, including the smaller exosomes and larger microvesicles, have the potential to reprogram a diversity of cells in the tumor microenvironment, by transferring various biomolecules in a cell-specific manner. Insights into the various biomolecules packed in EwS EVs as cargos and the molecular changes they trigger in recipient cells of the tumor microenvironment will shed light on various potential targets for therapeutic intervention in EwS. This review details EwS EVs composition, their potential role in metastasis and in the reprogramming of various cells of the tumor microenvironment, and the potential for clinical intervention.https://www.frontiersin.org/articles/10.3389/fcell.2021.726205/fullEwing sarcomatumor microenvironmentreprogrammingimmunosuppressionmetastasisextracellular vesicles |
| spellingShingle | Manideep C. Pachva Manideep C. Pachva Horton Lai Horton Lai Andy Jia Andy Jia Melanie Rouleau Melanie Rouleau Poul H. Sorensen Poul H. Sorensen Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment Frontiers in Cell and Developmental Biology Ewing sarcoma tumor microenvironment reprogramming immunosuppression metastasis extracellular vesicles |
| title | Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment |
| title_full | Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment |
| title_fullStr | Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment |
| title_full_unstemmed | Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment |
| title_short | Extracellular Vesicles in Reprogramming of the Ewing Sarcoma Tumor Microenvironment |
| title_sort | extracellular vesicles in reprogramming of the ewing sarcoma tumor microenvironment |
| topic | Ewing sarcoma tumor microenvironment reprogramming immunosuppression metastasis extracellular vesicles |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.726205/full |
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