Exosomes promote the invasion and metastasis of hepatocellular carcinoma cells via an integrin-dependent manner in the spleen-deficient state

Background: To investigate the detailed mechanism underlying the pro-metastatic effect of spleen deficiency (SD) syndrome on hepatocellular carcinoma (HCC). Methods: In the present study, our model was established based on an HCC mouse model induced by diethylnitrosamine using reserpine to induce SD. Exosomes were isolated and purified from mouse plasma samples using an exosome isolation kit. Subsequently, we verified the pro-metastatic effects of exosomes from the HCC mice with SD on HCC cells by transwell assays, wound healing assays, phalloidin staining in vitro, and lung metastasis assay of mice in vivo. Finally, we further explored the detailed mechanism underlying the pro-metastatic effect of exosomes from the HCC mice with SD on HCC cells. Results: We found that SD promoted the malignant progression of HCC in mice. Exosomes from HCC mice with SD enhanced the invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, upregulation of integrin & alpha;1, integrin & beta;1, and integrin & beta;5 seemed to play a key role in mediating the pro-metastatic effect of exosomes isolated from the HCC mice with SD, which was largely abrogated upon co-treatment with a broad-spectrum integrin inhibitor. Conclusion: Our findings demonstrated that exosomes promote the invasion and metastasis of HCC cells via an integrin-dependent manner in the spleen-deficient state that would contribute to our better understanding of the role of SD in HCC progression in traditional Chinese medicine, and thus management of the disease.