title: Metastatic properties of prostate cancer cells are controlled by VEGF.
abstract: Mechanisms of metastasis, the major complication of prostate cancer, are poorly understood. In this study, we define molecular mechanisms that may contribute to the highly invasive potential of prostate cancer cells. Vascular endothelial growth factor (VEGF), its receptors (VEGFRs), and alpha5beta1 integrin were expressed by prostate cancer cells in vitro and by prostate tumors in vivo, and their expression was elevated at sites of bone metastasis compared to original prostate tumor. VEGF, through interaction with its receptors, regulated adhesive and migratory properties of the cancer cells. Specifically, the highly metastatic prostate cancer cell subline LNCaP-C4-2 showed a decreased adhesive but an enhanced migratory response to fibronectin, a ligand for alpha5beta1 integrin, compared to its nonmetastatic counterpart. A similar pattern was also observed when bone sialoprotein was used as a ligand in migration assays. Increased migration of metastatic prostate cancer cells to fibronectin and bone sialoprotein was regulated by VEGF via VEGFR-2. Tumor suppressor PTEN was involved in control of VEGF/VEGFR-2 stimulated prostate cancer cell adhesion as well as proliferation.
authors.affiliation: Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Departments of Molecular Cardiology, Cardiology and Taussig Cancer Center, Cleveland Clinic Foundation, NB50, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Juhua
authors.initials: J
authors.lastname: Chen
authors.forename: Sarmishtha
authors.initials: S
authors.lastname: De
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brainard
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Byzova
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D039081:Integrin alpha5beta1 / Q000032:analysis / Q000235:genetics / Q000502:physiology; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000494:pharmacology / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000235:genetics / Q000502:physiology
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human