Role of nitric oxide in pancreatic cancer cells exhibiting the invasive phenotype

Publication date: Available online 6 March 2019Source: Redox BiologyAuthor(s): Mayumi Fujita, Veena Somasundaram, Debashree Basudhar, Robert Y.S. Cheng, Lisa A. Ridnour, Harumi Higuchi, Kaori Imadome, Jae Hong No, Gaurav Bharadwaj, David A. WinkAbstractPancreatic cancer is a highly metastatic tumor with an extremely low 5-year survival rate. Lack of efficient diagnostics and dearth of effective therapeutics that can target the cancer as well as the microenvironment niche are the reasons for limited success in treatment and management of this disease. Cell invasion through extracellular matrix (ECM) involves the complex regulation of adhesion to and detachment from ECM and its understanding is critical to metastatic potential of pancreatic cancer. To understand the characteristics of these cancer cells and their ability to metastasize, we compared human pancreatic cancer cell line, PANC-1 and its invading phenotype (INV) collected from transwell inserts. The invasive cell type, INV, exhibited higher resistance to Carbon-ion radiation compared to whole cultured (normally dish-cultured) PANC-1 (WCC), and had more efficient in vitro spheroid formation capability. Invasiveness of INV was hampered by nitric oxide synthase (NOS) inhibitors, suggesting that nitric oxide (NO) plays a cardinal role in PANC-1 invasion. In addition, in vitro studies indicated that a MEK-ERK-dependent, JAK independent mechanism through which NOS/NO modulate PANC-1 invasiveness. Suspended INV showed enhanc...
Source: Redox Biology - Category: Biology Source Type: research