Omental Tissue-Mediated Tumorigenesis of Gastric Cancer Peritoneal Metastases

The peritoneal cavity, especially the omentum, is a common site for gastric cancer metastasis, representing advanced disease stage and poor prognosis. Here, we studied the effects of omental tissue on gastric cancer tumor progression in vitro and in vivo. Utilizing in vitro models, we found that omental tissue secreted factors increased gastric cancer cellular growth (by 30–67%, P < 0.05), motility (>8-fold, P < 0.05), invasiveness (>7-fold, P < 0.05) and chemoresistance to platinum-based chemotherapeutic agents (>1.2-fold for oxaliplatin and >1.6-fold for cisplatin, P < 0.05). Using a robust proteomic approach, we identified numerous molecules secreted into the omental tissue conditioned medium (CM) which may promote gastric cancer cellular aggressiveness (i.e., IL-6, IL-8, MMP9, FN1, and CXCL-5). Next, an in vivo xenograft mouse model showed an increased human gastric adenocarcinoma tumor volume of cells co-cultured with human omental tissue secreted factors; 1.6 ± 0.55 vs. 0.3 ± 0.19 cm3 (P < 0.001), as well as increased angiogenesis. Finally, exosomes were isolated from human omental tissue CM of gastric cancer patients. These exosomes were taken up by gastric cancer cells enhancing their growth (>8-fold, P < 0.01) and invasiveness (>8-fold, P < 0.001). Proteomic analysis of the content of these exosomes identified several established cancer- related proteins (i.e., IL-6, IL-8, ICAM-1, CCl2, and OSM). Taken together, our findings...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research