Tumor-derived exosomes promote tumor growth through the modulation of RCAN1.4

Abstract

Intercellular communication between cells and their microenvironment is important for tumor growth. Exosomes are released from almost all cell types, including tumor cells. Tumor-derived exosomes have recently received a great deal of attention because of their ability to induce an aggressive phenotype, immune escape, angiogenesis and drug resistance through the horizontal transfer of cellular macromolecules between cancer cells. Here we showed that the only of A549 cell-released exosomes promote an angiogenic phenotype in HUVECs compared to other lung cancer cell-released exosomes. Using a miRNA array approach, we identified that specific miRNAs can modulate angiogenesis in A549 cell-released exosomes. Among these miRNAs, miRNA-619-5p significantly induced angiogenesis in HUVECs. We found that miRNA-619-5p directly targeted RCAN1.4 and ectopic expression of miRNA-619-5p markedly decreased RCAN1.4 expression. In patients with non-small cell lung cancer (NSCLC), the level of RCAN1.4 was significantly lower in cancer tissues than normal lung tissues, whereas the level of miRNA-619-5p was a significantly higher in cancer tissues than normal lung tissues. We also found that there was a significant inverse correlation between the expression of miRNA-619-5p and that of RCAN1.4. In addition, miRNA-619-5p expression was higher in exosomes isolated from plasma of patients with NSCLC than normal. The level of RCAN1.4 was associated with survival of patients with NSCLC. Thus, it might be possible for the level of miRNA-619-5p within exosome to be a utilized as a diagnosis and prognostic indicator for NSCLC patients. We are searching for the detailed mechanisms of angiogenesis and tumor growth through the modulation of RCAN1.4.