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Exosomes expressing carbonic anhydrase 9 promote angiogenesis
Kengo Horie1, Kyojiro Kawakami2, Yasunori Fujita2
1Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan.
Biochemical and Biophysical Research Communications
|August 31, 2017
Summary
Hypoxic renal cell carcinoma (RCC) releases exosomes containing carbonic anhydrase 9 (CA9). These CA9 exosomes promote angiogenesis and MMP2 expression, potentially driving cancer progression.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Exosomes play roles in the tumor microenvironment.
- Carbonic anhydrase 9 (CA9), induced by hypoxia-inducible factor 1 (HIF1), is overexpressed in cancers like renal cell carcinoma (RCC).
Purpose of the Study:
- To investigate the presence and function of CA9 in exosomes derived from RCC cells.
- To determine the effect of CA9-carrying exosomes on angiogenesis and related factors.
Main Methods:
- Quantified CA9 expression in RCC cell lines and isolated exosomes.
- Utilized hypoxia and CoCl2 to induce CA9 expression.
- Generated CA9-expressing HEK293 cells and co-cultured exosomes with human umbilical vein endothelial cells (HUVEC).
- Performed in vitro angiogenesis assays and measured MMP2 expression.
Main Results:
- OSRC-2 cells showed higher basal CA9 levels and secreted CA9 in exosomes.
- Hypoxia increased exosomal CA9 levels across cell lines.
- CA9 exosomes were taken up by HUVECs and promoted their migration and tube formation.
- CA9 exosomes upregulated MMP2 expression in HUVECs.
Conclusions:
- CA9 exosomes released by hypoxic RCC cells may enhance angiogenesis.
- These CA9 exosomes could contribute to tumor progression by promoting angiogenesis and MMP2 expression in the tumor microenvironment.
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