21P - Identification of the novel molecules mediating gastric cancer invasion based on genomic analysis of cancer-associated fibroblasts

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Basic Science
Gastric Cancer
Presenter Takatsugu Ishimoto
Citation Annals of Oncology (2016) 27 (suppl_9): ix1-ix8. 10.1093/annonc/mdw573
Authors T. Ishimoto1, K. Miyake2, T. Nandi1, M. Yashiro3, K.K. Huang1, K. Arima2, D. Izumi2, Y. Baba2, H. Baba2, P. Tan1
  • 1Cancer And Stem Cell Biology, Duke-NUS Graduate Medical School, 169857 - Singapore/SG
  • 2Department Of Gastroenterological Surgery, Kumamoto University, 860-8556 - Kumamoto/JP
  • 3Department Of Surgical Oncology, Osaka City University Medical School, 545-8585 - Osaka/JP

Abstract

Background

Cancer-associated fibroblasts (CAFs) have been reported to promote various types of tumor through secretion of soluble factors. However, there have been no systematic studies of CAFs in diffuse-type gastric cancers (DGCs). We investigated the characteristics and functional roles of CAFs in DGCs using comprehensive genomic approach.

Methods

Normal fibroblasts (NFs)/CAFs were subjected to Exome and RNA sequencing, and the possible candidates for functional assay were selected from among the acquired comprehensive data. The candidate molecules were examined the functional roles for GC tumor progression by in vitro assays.

Results

The differential expression analysis revealed that the expression of 34 genes were significantly up-regulated in CAFs compared with those in NFs. Furthermore, the pathway analysis showed that cytoskeletal signaling pathway was up-regulated and TGFb1 played crucial roles as one of upstream regulators in CAFs. Real-time imaging showed that the motility of CAFs was significantly greater on extracellular matrix. Intriguingly, the motility of CAFs conferred invasiveness on GC cells co-cultured with CAFs.

Conclusions

Comprehensive genomic analyses revealed that CAFs show an invasive molecular pattern. The findings in current study also suggests that CAFs in DGCs exhibit a particular motility associated with TGFb1 signaling and are intimately involved in GC invasion.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

Japan Society for the Promotion of Science (JSPS), KAKENHI Grant

Disclosure

All authors have declared no conflicts of interest.