Gastric cancer cell adhesion to laminin enhances acquired chemotherapeutic drug resistance mediated by MGr1-Ag/37LRP.

Abstract

Adhesion of cancer cells to the extracellular matrix (ECM) causes a novel acquired chemotherapeutic drug‑resistant phenotype, referred to as cell adhesion-mediated drug resistance (CAM-DR). Our previous studies suggested that the adhesion molecule MGr1-Ag/37LRP may promote multidrug resistance in gastric cancer cells. Therefore, we investigated MGr1-Ag/37LRP binding-induced adhesion, and its role in CAM-DR. Initial studies revealed that, after adhesion to the ECM, the multidrug-resistant gastric cancer cell lines SGC7901/VCR and SGC7901/ADR showed significantly higher mean adhesive cell numbers than non‑resistant SGC7901 cells. We then investigated expression of MGr1-Ag/37LRP in gastric cancer cells adhering to laminin. Western blotting, RT-PCR and dual-luciferase reporter assays showed that laminin induced MGr1-Ag/37LRP expression and activity. In vitro and in vivo assays revealed that small interfering RNA against MGr1-Ag/37LRP significantly reduced CAM-DR in SGC7901/VCR cells. In vivo and in vitro analyses revealed that binding of MGr1-Ag/37LRP decreased intracellular drug accumulation by increasing P-glycoprotein and multidrug-associated protein expression, and inhibited drug-induced apoptosis by regulating Bcl-2 and Bax expression. These results indicate that MGr1-Ag/37LRP contributes to laminin-mediated CAM-DR in gastric cancer cells, and is a potentially effective target for reversing this phenomenon in gastric cancer.

• Authors: Li Sun, Lili Liu, Xiangqiang Liu, Yafang Wang, Mengbin Li, Liping Yao, Jianjun Yang, Genlin Ji, Changcun Guo, Yanglin Pan, Shuhui Liang, Biaoluo Wang, Jie Ding, Hongwei Zhang, Yongquan Shi
• Journal: Oncology reports (Oncol Rep) Vol. 32 Issue 1 Pg. 105-14 (Jul 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 24840404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents, Phytogenic
• Laminin
• MGr1-antigen, human
• Vincristine

Topics

• Animals
• Antigens, Neoplasm (genetics, metabolism)
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Apoptosis (drug effects)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Drug Resistance, Neoplasm (drug effects)
• Extracellular Matrix (metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Laminin (metabolism)
• Mice
• Mice, Nude
• Neoplasms, Experimental
• Stomach Neoplasms (drug therapy, genetics, pathology)
• Vincristine (therapeutic use)