WB 03. Bacterial Endotoxin Enhances Metastatic Colonisation and Liver Metastasis in Colon Cancer Cells via Nox Derived H2O2
D. O’leary, J. Wang, T. Cotter, H. Redmond
Chair(s): Mustafa Cikirikcioglu, Frank Dor, Attila Szijarto, David J. Hackam, Cliff Shearman, Modise Koto, Yuzo Yamamoto
9:42 - 9:56h
at Erszebet Room (A)
Categories: Walter Brendel Award, Surgical Oncology
Session: Walter Brendel Award
Background
Nox-derived reactive oxygen species (ROS) phosphorylate redox sensitive pathways facilitating metastasis. Mediators of surgery-induced inflammation including lipopolysaccharide (LPS) activate Nox enzymes. Surgery-induced inflammation is associated with accelerated tumour growth. Thus we aimed to characterise the potential role for Nox-derived ROS in enhancing metastatic colonisation and liver metastasis in response to LPS.
Material and Methods
Balb/C mice underwent an intra-splenic injection of 2x105 pre-treated murine colon cancer CT-26 cells. There were four groups of pre-treated cells – untreated, LPS, LPS + DPI(Nox inhibitor), LPS + DMSO (n=8/group). Metastatic burden in the liver was assessed by counting surface liver nodules and liver/body weight ratio at day 7 post injection. Mitotic index was assessed using hematoxylin and eosin histology. Metastatic colonisation was assessed in vitro using SW480 cells in migration and invasion assays. ROS characterisation was examined using intracellular probes.
Result
LPS treated cells had enhanced liver metastatic burden compared to untreated cells (p=0.036). DPI successfully attenuated metastatic tumour growth compared to untreated and LPS treated groups (p<0.001). Nox inhibition successfully reduced proliferation in vivo (p=0.002) and, migration (p=0.027), invasion (p=0.041) and epithelial-mesenchymal transition in vitro. Using multiphoton microscopy, endoplasmic reticulum was the intracellular organelle responsible for Nox-generated ROS in response to LPS. Characterisation of the Nox-generated ROS identified H2O2 as the species responsible for facilitating spontaneous and accelerated tumour growth.
Conclusion
Targeting Nox generated H2O2 significantly attenuates spontaneous and accelerated metastatic tumour growth
