Gastric-cancer-derived mesenchymal stem cells: a promising target for resveratrol in the suppression of gastric cancer metastasis.

Abstract

The tumor microenvironment (TM) is an essential factor of tumor progression. Mesenchymal stem cells (MSCs) are important components of the TM and play critical roles in cancer metastasis. Resveratrol (RES) is a potential antitumor drug that has attracted extensive attention. However, it remains unclear whether RES can exert its antitumor activity by targeting MSCs located in the TM. In this study, we demonstrated that the conditioned medium of gastric-cancer-derived MSCs (GC-MSCs) promoted gastric cancer (GC) metastasis and facilitated the progression of epithelialmesenchymal transition (EMT) of GC cells. However, after pretreatment with RES, the prometastatic effect of GC-MSCs on GC cells was reversed. Furthermore, RES reduced GC-MSC (IL-6, IL-8, MCP-1, VEGF) gene expression and protein secretion, and counteracted the activation of the GC-MSC-induced Wnt/β-catenin signaling of GC cells, with less β-catenin nuclear transport and declined expression of β-catenin, CD44, and CyclinD3 in GC cells. Re-expression of β-catenin impaired the inhibitory effect of RES on GC cells. In conclusion, RES restricted the mobility increase of GC cells and reversed the progress of EMT induced by GC-MSCs by inactivating the Wnt/β-catenin signaling. GC-MSCs are promising target for RES in the inhibition of GC metastasis.

• Authors: Lei Yin, Rongxue Zhang, Yuyan Hu, Wenhao Li, Maoye Wang, Zhaofeng Liang, Zixuan Sun, Runbi Ji, Wenrong Xu, Hui Qian
• Journal: Human cell (Hum Cell) Vol. 33 Issue 3 Pg. 652-662 (Jul 2020) ISSN: 1749-0774 [Electronic] Japan
• PMID: 32350750 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• CCL2 protein, human
• Chemokine CCL2
• Interleukin-6
• Interleukin-8
• Wnt Proteins
• beta Catenin
• Resveratrol

Topics

• Antineoplastic Agents, Phytogenic
• Cell Line, Tumor
• Chemokine CCL2 (genetics, metabolism)
• Gene Expression (drug effects)
• Humans
• Interleukin-6 (genetics, metabolism)
• Interleukin-8 (genetics, metabolism)
• Mesenchymal Stem Cells (pathology, physiology)
• Molecular Targeted Therapy
• Neoplasm Metastasis (drug therapy)
• Phytotherapy
• Resveratrol (therapeutic use)
• Stomach Neoplasms (drug therapy, genetics, pathology)
• Tumor Microenvironment
• Wnt Proteins (metabolism)
• beta Catenin (genetics, metabolism)