Generation of a Syngeneic Mouse Model to Study the Effects of Vascular Endothelial Growth Factor in Ovarian Carcinoma
Open accessAbstract
Vascular endothelial growth factor (VEGF) performs multifaceted functions in the tumor microenvironment promoting angiogenesis, suppressing anti-tumor immune response, and possibly exerting autocrine functions on tumor cells. However, appropriate syngeneic animal models for in vivo studies are lacking. Using retroviral transfection and fluorescence-activated cell sorting, we generated a C57BL6 murine ovarian carcinoma cell line that stably overexpresses the murine VEGF164 isoform and the enhanced green fluorescent protein. VEGF164 overexpression dramatically accelerated tumor growth and ascites formation, significantly enhanced tumor angiogenesis, and substantially promoted the survival of tumor cells in vivo. In vitro, VEGF164 overexpression significantly enhanced cell survival after growth factor withdrawal and conferred resistance to apoptosis induced by cis-platin through an autocrine mechanism. VEGF/green fluorescent protein-expressing tumors were not recognized by the adaptive immune system. After vaccination, a specific anti-tumor T-cell response was detected, but tumor growth was not inhibited. This engineered murine carcinoma model should prove useful in the investigation of the role of VEGF in modulating the tumor microenvironment and affecting the complex interactions among angiogenesis mechanisms, anti-tumor immune mechanisms, and tumor cell behavior at the natural state or during therapy in ovarian carcinoma.
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Syngeneic mouse models transplant mouse cell lines into a recipient from the same genetic background, enabling the study of immune response, immunotherapies and tumor vascularization.
“Syngeneic mouse models transplant mouse cell lines into a recipient from the same genetic background, enabling the study of immune response, immunotherapies and tumor vascularization (Zhang et al., 2002; Yu et al., 2018).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Zhang et al., 2002
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References 77 · Cited by 151
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- Authors
- Zhang, L., Yang, N., Conejo Garcia, J.-R., Mohamed, A., Benencia, F., Rubin, S. C., Allman, D., & Coukos, G.
- Affiliations
- University of Pennsylvania (US)
- Abramson Cancer Center (US)
- Corresponding author
- Coukos, George
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2002-12
- Volume
- 161
- Issue
- 6
- Pages
- 2295-2309
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1850900
- OpenAlex
- W2114195790
- Cited by
- 151
- References
- 77
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 1 · 2023: 7 · 2022: 9 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 11 · 2013: 5 · 2012: 6
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fogarty International Center
- National Institute of Child Health and Human Development
- National Cancer Institute (CA 83638)
- National Institutes of Health (D43 TW00671)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- vascular endothelial growth factor, VEGF164, ovarian carcinoma, syngeneic mouse model, tumor angiogenesis, tumor microenvironment, antitumor immunity, autocrine signaling, cisplatin resistance, apoptosis, tumor cell survival, tumor growth, ascites, cancer vaccination, T cell response, retroviral transfection, C57BL/6 mice
- MeSH terms
- Animals, Antineoplastic Agents, Ascites, Carcinoma, Cell Separation, Cisplatin, Disease Models, Animal, Female, Flow Cytometry, Humans, Immunohistochemistry, Luminescent Proteins, Lymphokines, Mice, Inbred C57BL, Neoplasm Metastasis, Neoplasm Transplantation, Neovascularization, Pathologic, Ovarian Neoplasms, Peritoneal Neoplasms, Recombinant Fusion Proteins, Tumor Cells, Cultured, Endothelial Growth Factors, Apoptosis, Cell Transplantation, Cancer Vaccines, Protein Isoforms, In Situ Nick-End Labeling, Intercellular Signaling Peptides and Proteins, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Green Fluorescent Proteins, Mice
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