Human macrophage-engineered vesicles for utilization in ovarian cancer treatment
BackgroundOvarian cancer is a deadly female malignancy with a high rate of recurrent and chemotherapy-resistant disease. Tumor-associated macrophages (TAMs) are a significant component of the tumor microenvironment and include high levels of M2-protumor macrophages that promote chemoresistance and m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1042730/full |
| _version_ | 1797956014892384256 |
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| author | David Schweer Namrata Anand Namrata Anand Abigail Anderson J. Robert McCorkle Khaga Neupane Alexandra N. Nail Brock Harvey Kristen S. Hill Frederick Ueland Christopher Richards Jill Kolesar Jill Kolesar |
| author_facet | David Schweer Namrata Anand Namrata Anand Abigail Anderson J. Robert McCorkle Khaga Neupane Alexandra N. Nail Brock Harvey Kristen S. Hill Frederick Ueland Christopher Richards Jill Kolesar Jill Kolesar |
| author_sort | David Schweer |
| collection | DOAJ |
| description | BackgroundOvarian cancer is a deadly female malignancy with a high rate of recurrent and chemotherapy-resistant disease. Tumor-associated macrophages (TAMs) are a significant component of the tumor microenvironment and include high levels of M2-protumor macrophages that promote chemoresistance and metastatic spread. M2 macrophages can be converted to M1 anti-tumor macrophages, representing a novel therapeutic approach. Vesicles engineered from M1 macrophages (MEVs) are a novel method for converting M2 macrophages to M1 phenotype-like macrophages.MethodsMacrophages were isolated and cultured from human peripheral blood mononuclear cells. Macrophages were stimulated to M1 or M2 phenotypes utilizing LPS/IFN-γ and IL-4/IL-13, respectively. M1 MEVs were generated with nitrogen cavitation and ultracentrifugation. Co-culture of ovarian cancer cells with macrophages and M1 MEVs was followed by cytokine, PCR, and cell viability analysis. Murine macrophage cell line, RAW264.7 cells were cultured and used to generate M1 MEVs for use in ovarian cancer xenograft models.ResultsM1 MEVs can effectively convert M2 macrophages to an M1-like state both in isolation and when co-cultured with ovarian cancer cells in vitro, resulting in a reduced ovarian cancer cell viability. Additionally, RAW264.7 M1 MEVs can localize to ovarian cancer tumor xenografts in mice.ConclusionHuman M1 MEVs can repolarize M2 macrophages to a M1 state and have anti-cancer activity against ovarian cancer cell lines. RAW264.7 M1 MEVs localize to tumor xenografts in vivo murine models. |
| first_indexed | 2024-04-10T23:42:10Z |
| format | Article |
| id | doaj.art-0c65814e8e6c4b9799df4456fabbb36e |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T23:42:10Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0c65814e8e6c4b9799df4456fabbb36e2023-01-11T05:54:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.10427301042730Human macrophage-engineered vesicles for utilization in ovarian cancer treatmentDavid Schweer0Namrata Anand1Namrata Anand2Abigail Anderson3J. Robert McCorkle4Khaga Neupane5Alexandra N. Nail6Brock Harvey7Kristen S. Hill8Frederick Ueland9Christopher Richards10Jill Kolesar11Jill Kolesar12Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Medicine, University of Kentucky, Lexington, KY, United StatesMarkey Cancer Center, University of Kentucky, Lexington, KY, United StatesDepartment of Pharmacy and Practice, College of Pharmacy, University of Kentucky, Lexington, KY, United StatesMarkey Cancer Center, University of Kentucky, Lexington, KY, United StatesMarkey Cancer Center, University of Kentucky, Lexington, KY, United StatesDepartment of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, KY, United StatesDepartment of Pharmacy and Practice, College of Pharmacy, University of Kentucky, Lexington, KY, United StatesDepartment of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, KY, United StatesMarkey Cancer Center, University of Kentucky, Lexington, KY, United StatesDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Medicine, University of Kentucky, Lexington, KY, United StatesDepartment of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, KY, United StatesDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Medicine, University of Kentucky, Lexington, KY, United StatesDepartment of Pharmacy and Practice, College of Pharmacy, University of Kentucky, Lexington, KY, United StatesBackgroundOvarian cancer is a deadly female malignancy with a high rate of recurrent and chemotherapy-resistant disease. Tumor-associated macrophages (TAMs) are a significant component of the tumor microenvironment and include high levels of M2-protumor macrophages that promote chemoresistance and metastatic spread. M2 macrophages can be converted to M1 anti-tumor macrophages, representing a novel therapeutic approach. Vesicles engineered from M1 macrophages (MEVs) are a novel method for converting M2 macrophages to M1 phenotype-like macrophages.MethodsMacrophages were isolated and cultured from human peripheral blood mononuclear cells. Macrophages were stimulated to M1 or M2 phenotypes utilizing LPS/IFN-γ and IL-4/IL-13, respectively. M1 MEVs were generated with nitrogen cavitation and ultracentrifugation. Co-culture of ovarian cancer cells with macrophages and M1 MEVs was followed by cytokine, PCR, and cell viability analysis. Murine macrophage cell line, RAW264.7 cells were cultured and used to generate M1 MEVs for use in ovarian cancer xenograft models.ResultsM1 MEVs can effectively convert M2 macrophages to an M1-like state both in isolation and when co-cultured with ovarian cancer cells in vitro, resulting in a reduced ovarian cancer cell viability. Additionally, RAW264.7 M1 MEVs can localize to ovarian cancer tumor xenografts in mice.ConclusionHuman M1 MEVs can repolarize M2 macrophages to a M1 state and have anti-cancer activity against ovarian cancer cell lines. RAW264.7 M1 MEVs localize to tumor xenografts in vivo murine models.https://www.frontiersin.org/articles/10.3389/fonc.2022.1042730/fullovarian cancertumor-associated macrophage (TAMs)M1 macrophageM2 macrophagevesicleimmunotherapy |
| spellingShingle | David Schweer Namrata Anand Namrata Anand Abigail Anderson J. Robert McCorkle Khaga Neupane Alexandra N. Nail Brock Harvey Kristen S. Hill Frederick Ueland Christopher Richards Jill Kolesar Jill Kolesar Human macrophage-engineered vesicles for utilization in ovarian cancer treatment Frontiers in Oncology ovarian cancer tumor-associated macrophage (TAMs) M1 macrophage M2 macrophage vesicle immunotherapy |
| title | Human macrophage-engineered vesicles for utilization in ovarian cancer treatment |
| title_full | Human macrophage-engineered vesicles for utilization in ovarian cancer treatment |
| title_fullStr | Human macrophage-engineered vesicles for utilization in ovarian cancer treatment |
| title_full_unstemmed | Human macrophage-engineered vesicles for utilization in ovarian cancer treatment |
| title_short | Human macrophage-engineered vesicles for utilization in ovarian cancer treatment |
| title_sort | human macrophage engineered vesicles for utilization in ovarian cancer treatment |
| topic | ovarian cancer tumor-associated macrophage (TAMs) M1 macrophage M2 macrophage vesicle immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1042730/full |
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