RT Journal Article
SR Electronic
T1 Rab27b, a Regulator of Exosome Secretion, Is Associated With Peritoneal Metastases in Gastric Cancer
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 30
OP 39
DO 10.21873/cgp.20362
VO 20
IS 1
A1 SHO NAMBARA
A1 TAKAAKI MASUDA
A1 KOSUKE HIROSE
A1 QINGJIANG HU
A1 TARO TOBO
A1 YUKI OZATO
A1 JUNJI KURASHIGE
A1 YOSHIKI HIRAKI
A1 YUICHI HISAMATSU
A1 TOMOHIRO IGUCHI
A1 KEISHI SUGIMACHI
A1 EIJI OKI
A1 TOMOHARU YOSHIZUMI
A1 KOSHI MIMORI
YR 2023
UL http://cgp.iiarjournals.org/content/20/1/30.abstract
AB Background/Aim: Peritoneal metastasis (PM) of gastric cancer (GC) leads to poor clinical outcomes. Tumor-derived exosomes promote metastasis via communication between tumor cells and host cells. In this study, we investigated the effect of Rab27, which is required for exosome secretion, on the PM of GC. Materials and Methods: We established a stable knockdown of two Rab27 homologs, Rab27a and Rab27b, in human GC cells (58As9) with a high potential of PM. We examined the level of exosome secretion from Rab27-knockdown 58As9 cells by Western blotting and the ability of Rab27b knockdown to suppress PM in 58As9 cells using a mouse xenograft model. In vitro proliferation and invasion assays were performed in the Rab27b-knockdown cells. Next, Rab27b expression was evaluated in human GC tissues by immunohistochemistry. Finally, we assessed the clinicopathological and prognostic significance of Rab27b expression by RT-qPCR in both our and other TCGA datasets of GC. Results: Rab27a and Rab27b knockdown in 58As9 cells decreased the secretion of exosomes, characterized by the endocytic marker CD63. Rab27b knockdown decreased PM in vivo without affecting the in vitro proliferation or invasion ability of 58As9 cells. In human GC tissues, Rab27b was overexpressed in tumor cells. The overall and recurrence-free survival rates were significantly lower in GC patients with high compared to low Rab27b mRNA expression in our and other TCGA datasets. Conclusion: Rab27b expression potentially serves as a poor prognostic biomarker, possibly affecting PM via exosome secretion from GC cells.