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Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro
Published on: November 26, 2018
Circulating monocytes expressing CD31: implications for acute and chronic angiogenesis
Sun-Jin Kim1, Jang-Seong Kim, John Papadopoulos
1Department of Cancer Biology, Cancer MetastasisResearch Center, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:
To identify the roles of various circulating cells (eg, endothelial and/or stem and progenitor cells) in angiogenesis, we parabiosed a wild-type syngeneic mouse with a transgenic syngeneic green fluorescent protein mouse. Following the establishment of a common circulation between these parabionts, we investigated acute (7 to 10 days), subacute (2 to 3 weeks), and chronic (4 to 6 weeks) phases of angiogenesis in wild-type mice using wound healing, implanted gel foam fragments, and subcutaneous tumor assays, respectively. We found that under in vitro conditions, circulating murine monocytes expressed F4/80, CD31, and vascular endothelial growth factor receptor 2, but neither CD133 nor von Willebrand factor, whereas murine endothelial cells expressed CD31, vascular endothelial growth factor receptor 2, and von Willebrand factor, but neither CD133 nor F4/80. Immunofluorescence analysis revealed that green fluorescent protein-positive cells in the walls of new vessels in wounds, gel foam blocks, and tumors expressed both F4/80 and CD31, that is, macrophages. Pericytes, cells that express both CD31 and desmin, were found both in the walls of tumor-associated vessels and within tumors. Collectively, these data demonstrate that monocytes (ie, cells that express both CD31 and F4/80) may be recruited to the site of tissue injury and directly contribute to angiogenesis, reaffirming the close relationships between various cell types within the reticuloendothelial system and suggesting possible targets for anticancer treatments.
Insights
Monocytes, identified by CD31 and F4/80 markers, contribute to new blood vessel formation (angiogenesis) in response to tissue injury. This finding highlights potential therapeutic targets for cancer treatment.
Area of Science:
- Cell Biology
- Immunology
- Oncology
Background:
- Angiogenesis, the formation of new blood vessels, is crucial for tissue repair and tumor growth.
- The specific roles of circulating cells, such as endothelial cells, stem cells, and progenitor cells, in angiogenesis remain incompletely understood.
- Understanding these cellular contributions is vital for developing targeted therapies, particularly in cancer treatment.
Purpose of the Study:
- To elucidate the contributions of various circulating cells to the process of angiogenesis.
- To identify specific cell types involved in neovascularization during different phases of tissue repair and tumor development.
- To explore potential therapeutic targets for anticancer treatments based on cellular mechanisms of angiogenesis.
Main Methods:
- Parabiosis was established between wild-type and green fluorescent protein (GFP)-transgenic syngeneic mice to enable cell tracking.
- Angiogenesis was studied in acute, subacute, and chronic phases using wound healing, implanted gel foam, and subcutaneous tumor models, respectively.
- Immunofluorescence and in vitro analyses were performed to characterize cell markers (F4/80, CD31, VEGFR2, CD133, von Willebrand factor, desmin) on circulating and newly formed vascular cells.
Main Results:
- Circulating monocytes expressed F4/80, CD31, and VEGFR2, distinguishing them from endothelial cells which expressed CD31, VEGFR2, and von Willebrand factor.
- GFP-positive cells within newly formed vessels in all angiogenesis models were identified as macrophages (expressing F4/80 and CD31).
- Pericytes (CD31 and desmin positive) were observed in tumor-associated vessels and within tumors.
Conclusions:
- Monocytes expressing CD31 and F4/80 are recruited to sites of tissue injury and directly contribute to angiogenesis.
- These findings reinforce the interconnectedness of the reticuloendothelial system and vascular development.
- The direct role of monocytes in angiogenesis presents promising targets for novel anticancer therapies.
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