Background: Liver is the most frequent metastatic site of gastric cancer (GC), especially in patients with HER2 positive GC. Exosomal integrin αvβ5 has been shown to promote liver metastasis (LM), and the cross talk between integrins and HER2 during breast cancer metastasis has been reported. However, whether there's an association between HER2 and integrin αvβ5 (ITGAvB5), and whether their association has predictive value in GC liver metastasis (GCLM) remains unknown.
Methods: The association between ITGβ5 and HER2 were accessed by RT-PCR, western blot and ELISA. We tested the function of ITGβ5 on HER2 positive GC cells using Transwell assays and scratch assays. Besides, we detect ITGβ5 expression in tumor tissue of GC patients and exosomes derived from advanced GC to analyze the association between HER2 and LM.
Results: In our study, we found that ITGβ5, rather than ITGAV, was highly upregulated by HER2 through PI3K-AKT pathways in HER2 positive GC. Overexpression of ITGβ5 promoted the migration and invasion of HER2 positive GC cells in vitro. ITGβ5 was found to be an independent prognostic factor for GC. Besides, ITGβ5 level was only associated with LM. Detection of exosomal ITGβ5 and HER2 in the serum of GC patients revealed that exosomal ITGβ5 and HER2 levels are in accordance with that in tissue, and exosomal ITGβ5 level was higher in GCLM than other metastasis.
Conclusions: Our study demonstrated ITGβ5 is regulated and functions in accordance with HER2 in promoting GCLM. Exosomal ITGβ5 levels might be a potential liquid biopsy biomarker for GCLM.
Keywords: Gastric cancer (GC); HER2; integrin αvβ5; liver metastasis (LM).
2020 Annals of Translational Medicine. All rights reserved.