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.

PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

“…In cancer cells, the abnormal overexpression of 67LR induced the enhancement of metastasis and tumor growth through the overexpression of both cyclin-dependent kinases 1/2 and cyclins (A and B) 20 . Furthermore, 67LR induces an acquired chemotherapeutic drug-resistant phenotype 21 . Collectively, 67LR has an essential role in the development and maintenance of cancer.…”

Gastrin induces multidrug resistance via the degradation of p27Kip1 in the gastric carcinoma cell line SGC7901

“…First, in drug-resistant human myeloma cell lines, it was found that facilitation of Skp2 expression promoted cell cycle progression and suppressed p27 Kip1 expression (7). Second, cell adhesion-mediated drug resistance (CAM-DR) in many types of cancer is a primary factor leading to relapse after chemotherapy (8). It was demonstrated that increasing p27 Kip1 level or disturbing p27 Kip1 phosphorylation at Thr (187) inhibited CAM-DR in human myeloma cell lines (9) Third, Skp2 can promote the degradation of p27 Kip1 through the ubiquitin proteasome pathway (10), while the degradation of p27 Kip1 can also be increased by KPC (11).…”

“…In drug-resistant human myeloma cell lines, it was found that facilitation of S-phase kinase-associated protein 2 (Skp2) expression promoted cell cycle progression and p27 Kip1 degradation (7). Cell adhesion-mediated drug resistance (CAM-DR) is a primary factor leading to relapse after chemotherapy (8). It was demonstrated that increasing the p27 Kip1 level or disturbing p27 Kip1 phosphorylation at the Thr (187) site inhibited CAM-DR in human myeloma cell lines (9).…”

Gene expression profiling of epithelial ovarian cancer reveals key genes and pathways associated with chemotherapy resistance

“…There is a relationship between cell adhesion, which is known to protect cells from apoptosis, and drug resistance (Croix and Kerbel, 1997). Sun et al (2014) reported that gastric cancer cell adhesion to laminin enhances acquired chemotherapeutic drug resistance. Therefore, we speculated that cell adhesion was related to chemotherapy resistance in EOC.…”