Journal article
Human macrophage-engineered vesicles for utilization in ovarian cancer treatment
Frontiers in oncology, Vol.12, 1042730
01/11/2023
DOI: 10.3389/fonc.2022.1042730
PMCID: PMC9875020
PMID: 36713536
Abstract
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-gamma 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.
Details
- Title: Subtitle
- Human macrophage-engineered vesicles for utilization in ovarian cancer treatment
- Creators
- David Schweer - University of KentuckyNamrata Anand - University of KentuckyAbigail Anderson - Markey Cancer CenterJ. Robert McCorkle - University of KentuckyKhaga Neupane - University of KentuckyAlexandra N. Nail - University of KentuckyBrock Harvey - University of KentuckyKristen S. Hill - Markey Cancer CenterFrederick Ueland - University of KentuckyChristopher Richards - University of KentuckyJill Kolesar - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Frontiers in oncology, Vol.12, 1042730
- Publisher
- Frontiers Media Sa
- DOI
- 10.3389/fonc.2022.1042730
- PMID
- 36713536
- PMCID
- PMC9875020
- ISSN
- 2234-943X
- eISSN
- 2234-943X
- Number of pages
- 13
- Grant note
- T32CA160003 / NIH Training Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30 CA 177558 / Cancer Center Support Grant
- Language
- English
- Date published
- 01/11/2023
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695797302771
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