Cross-talk Between Gastric Cancer and Hepatic Stellate Cells Promotes Invadopodia Formation During Liver Metastasis

Overview

Journal Cancer Sci

Specialty Oncology

Date 2023 Dec 5

PMID 38050654

Authors

Chuanfu Ren

Zhi Yang

En Xu

Xing Kang

Xingzhou Wang

Qi Sun

Chao Wang

Liang Zhang

Ji Miao

Banxin Luo

Kai Chen

Song Liu

Xiaofei Shen

Xiaofeng Lu

Kai Yin

Meng Wang

Xuefeng Xia

Wenxian Guan

Affiliations

Soon will be listed here.

Abstract

In gastric cancer (GC), the liver is a common organ for distant metastasis, and patients with gastric cancer with liver metastasis (GCLM) generally have poor prognosis. The mechanism of GCLM is unclear. Invadopodia are special membrane protrusions formed by tumor cells that can degrade the basement membrane and ECM. Herein, we investigated the role of invadopodia in GCLM. We found that the levels of invadopodia-associated proteins were significantly higher in liver metastasis than in the primary tumors of patients with GCLM. Furthermore, GC cells could activate hepatic stellate cells (HSCs) within the tumor microenvironment of liver metastases through the secretion of platelet-derived growth factor subunit B (PDGFB). Activated HSCs secreted hepatocyte growth factor (HGF), which activated the MET proto-oncogene, MET receptor of GC cells, thereby promoting invadopodia formation through the PI3K/AKT pathway and subsequently enhancing the invasion and metastasis of GC cells. Therefore, cross-talk between GC cells and HSCs by PDGFB/platelet derived growth factor receptor beta (PDGFRβ) and the HGF/MET axis might represent potential therapeutic targets to treat GCLM.

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