title: Caveolin-1 regulates endothelial adhesion of lung cancer cells via reactive oxygen species-dependent mechanism.
abstract: The knowledge regarding the role of caveolin-1 (Cav-1) protein on endothelium adhesion of cancer cells is unclear. The present study revealed that Cav-1 plays a negative regulatory role on cancer-endothelium interaction. Endogenous Cav-1 was shown to down-regulate during cell detachment and the level of such a protein was conversely associated with tumor-endothelial adhesion. Furthermore, the ectopic overexpression of Cav-1 attenuated the ability of the cancer cells to adhere to endothelium while shRNA-mediated Cav-1 knock-down exhibited the opposite effect. We found that cell detachment increased cellular hydrogen peroxide and hydroxyl radical generation and such reactive oxygen species (ROS) were responsible for the increasing interaction between cancer cells and endothelial cells through vascular endothelial cell adhesion molecule-1 (VCAM-1). Importantly, Cav-1 was shown to suppress hydrogen peroxide and hydroxyl radical formation by sustaining the level of activated Akt which was critical for the role of Cav-1 in attenuating the cell adhesion. Together, the present study revealed the novel role of Cav-1 and underlying mechanism on tumor adhesion which explain and highlight an important role of Cav-1 on lung cancer cell metastasis.
authors: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, and Cell-based Drug and Health Product Development Research Unit, Chulalongkorn University, Bangkok, Thailand.
authors: Pithi
authors: P
authors: Chanvorachote
authors: Preedakorn
authors: P
authors: Chunhacha
mesh_terms: D051242:Caveolin 1 / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt