In another study investigating the association of hiTDExs with MMP functions in cancer models, Horie et al. found that hypoxia can upregulate MMP2 level by increasing CA9 expression in renal cell carcinoma (RCC)-derived exosomes, and thereby hiTDEx CA9 can in turn promote angiogenesis and migration of HUVEC cells in TME [27]. Here, CA9 is linked to hereditary clear cell renal cell carcinoma.