Silencing of Discoidin Domain Receptor-1 (DDR1) Concurrently Inhibits Multiple Steps of Metastasis Cascade in Gastric Cancer

Accumulating evidence suggests that a unique set of receptor tyrosine kinases, known as discoidin domain receptors (DDRs), plays a role in cancer progression by interacting with the surrounding collagen matrix. In this study, we investigated the expression and role of DDR1 in human gastric cancer metastasis. Proliferation, migration, invasion, and tube formation assays were conducted in DDR1-expressing MKN74 gastric cancer cells and corresponding DDR1-silenced cells. The effects of DDR1 on tumor growth and metastasis were examined in orthotopically implanted and experimental liver metastasis models in nude mice. The expression of DDR1 in surgical specimens was analyzed by immunohistochemistry. DDR1 was expressed in human gastric cancer cell lines, and its expression in human gastric tumors was associated with poor prognosis. Among seven gastric cancer cell lines, MKN74 expressed the highest levels of DDR1. DDR1-silenced MKN74 cells showed unaltered proliferation activity. In contrast, migration, invasion, and tube formation were significantly reduced. When examined in an orthotopic nude mouse model, DDR1-silenced implanted tumors significantly reduced angiogenesis and lymphangiogenesis, thereby leading to reductions in lymph node metastasis and liver metastasis. In a model of experimental liver metastasis, DDR1-silenced cells almost completely inhibited liver colonization and metastasis. DDR1 deficiency led to reduced expression of the genes encoding vascular endothelial growth factor (VEGF)-A, VEGF-C, and platelet-derived growth factor-B. These results suggest that DDR1 is involved in gastric cancer tumor progression and that silencing of DDR1 inhibits multiple steps of the gastric cancer metastasis process.     

Protective effect of cAMP on tumor promoter-mediated inhibition of cell-cell communication

The formation and maintenance of electrical cell coupling is inhibited by 100 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA). This inhibition could be prevented by db-cAMP and aminophylline when added together with TPA, though they did not restore the cell coupling once it had already been blocked by TPA. It is suggested that db-cAMP affects the early membrane effects of TPA in FL cells.     

Studies on enzymatic reduction of aliphatic nitro compounds: Reductive dimerization of β-nitrostyrene and 1-nitro-4-phenylbutadiene

Enzymatic reduction of aliphatic nitro compounds, β-nitrostyrene (I), 1-nitro-4-phenylbutadiene (II), 1-nitro-4-phenyl-1-butene (III), 1-nitro-2-phenylethane (IV), and nitrophenylethane (V) was investigated in a xanthine oxidase-hypoxanthine system. I and II were easily reduced by the enzyme system under anaerobic conditions, but III, IV, and V resisted to the enzymatic reduction. The reduction products of I and II were isolated from the reaction mixtures and were identified as dimolecular compounds, 1,4-dinitro-2, 3-diphenylbutane and 1,4-dinitro-2,3-distyrylbutane, respectively, by mass, nuclear magnetic resonance, and infrared spectrometries, and by elementary analyses.