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Exosomes expressing carbonic anhydrase 9 promote angiogenesis.

Abstract：

:Exosomes or microvesicles that are secreted from cells are considered to play important roles in tumor microenvironment. Carbonic anhydrase 9 (CA9), which is induced by hypoxia-inducible factor 1 (HIF1) in response to hypoxia, is overexpressed in many types of cancer including renal cell carcinoma (RCC). We examined the expression level of CA9 in several RCC cell lines and found that the basal level of CA9 was much higher in OSRC-2 cells than in Caki-1, KMRC-1 and 786-O cells. Consistent with the intracellular expression levels, CA9 was abundantly detected in exosomes isolated by ultracentrifugation from OSRC-2 cells. Density gradient centrifugation of OSRC-2 and 786-O exosomes confirmed the co-presence of CA9 with exosomal markers. Upon hypoxia and treatment with CoCl2, a hypoxia mimic agent, the CA9 level in exosomes was increased for all cell lines. In order to examine the effects of CA9 exosomes on angiogenesis, we generated stably transfected HEK293 cells expressing CA9. Immunocytochemical staining demonstrated the uptake of CA9 exosomes by human umbilical vein endothelial cells (HUVEC). In vitro angiogenesis assays using HUVEC revealed that CA9 exosomes promoted migration and tube formation. Lastly, MMP2 expression was increased by treatment with CA9 exosomes in HUVEC. Taken together, our results suggest the possibility that CA9 exosomes released from hypoxic RCC may enhance angiogenesis in microenvironment, thereby contributing to cancer progression.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Horie K,Kawakami K,Fujita Y,Sugaya M,Kameyama K,Mizutani K,Deguchi T,Ito M

doi

10.1016/j.bbrc.2017.08.107

subject

Has Abstract

pub_date

2017-10-21 00:00:00

pages

356-361

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)31690-X

journal_volume

492

pub_type

杂志文章

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