title: CD151 is associated with prostate cancer cell invasion and lymphangiogenesis in vivo.
abstract: CD151, a member of the tetraspanin family, is associated with regulation of migration of normal and tumour cells via cell surface microdomain formation. CD151 was found in our laboratory to have a prognostic value in prostate cancer and is a promoter of prostate cancer migration and invasion. These roles involve association with integrins on both cell-cell and cell-stroma levels. Furthermore, CD151 plays a role in endothelial cell motility. CD151 expression was examined in three commonly used prostate cancer cell lines. We investigated CD151 expression, angiogenesis (microvessel density; MVD) and lymphangiogenesis (lymphatic vessel density; LVD) in an orthotopic xenograft model of prostate cancer in matched tumours from primary and secondary sites. CD151 was found to be heterogeneously expressed across different prostate cancer cell lines and the levels of CD151 expression were significantly higher in the highly tumorigenic, androgen-insensitive cells PC-3 and DU-145 compared to the androgen-sensitive cell line LNCaP (P<0.05). The majority of in vivo xenografts developed pelvic lymph node metastases. Importantly, primary tumours that developed metastasis had significantly higher CD151 expression and MVD compared to those which did not develop metastasis (P<0.05). We identified, for the first time, that CD151 expression is associated with LVD in prostate cancer. These findings underscore the potential role of CD151 and angiogenesis in the metastatic potential of prostate cancer. CD151 has a prognostic value in this mouse model of prostate cancer and may play a role in lymphangiogenesis. CD151 is likely an important regulator of cancer cell communication with the surrounding microenvironment.
authors.affiliation: Clinical Pharmacology and Therapeutics Unit, Department of Medicine (Austin Health/Northern Health), The University of Melbourne, Heidelberg, VIC, Australia.
authors.forename: Sujitra
authors.initials: S
authors.lastname: Detchokul
authors.forename: Bradley
authors.initials: B
authors.lastname: Newell
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Williams
authors.forename: Albert G
authors.initials: AG
authors.lastname: Frauman
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000378:metabolism; D042583:Lymphangiogenesis / Q000235:genetics*; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D015398:Signal Transduction; D060185:Tetraspanin 24 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C554715:CD151 protein, human; D016023:Integrins; D060185:Tetraspanin 24