title: Knockout of the tetraspanin Cd9 in the TRAMP model of de novo prostate cancer increases spontaneous metastases in an organ-specific manner.
abstract: Prostate cancer is an extremely heterogeneous disease; patients that do progress to late-stage metastatic prostate cancer have limited treatment options, mostly palliative. Molecules involved in the metastatic cascade may prove beneficial in stratifying patients to assign appropriate treatment modalities and may also prove to be therapeutic antimetastatic targets. The tetraspanin group of molecules are integral membrane proteins that associate with motility-related proteins such as integrins. Clinical studies have mostly shown that reduced expression levels of the tetraspanin CD9 are correlated with tumour progression in a range of cancers. Furthermore, functional studies have shown CD9 to be involved in cell motility and adhesion and that it may influence metastasis. The effects of endogenous CD9 on prostate cancer initiation and progression were analysed by crossing a Cd9-/- (KO) murine model with a model of de novo developing and spontaneously metastasising prostate cancer, namely the transgenic adenocarcinoma of mouse prostate model. Our study demonstrates for the first time that ablation of Cd9 had no detectable effect on de novo primary tumour onset, but did significantly increase metastasis to the liver but not the lungs.
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle and Cancer Research Program, Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Ben T
authors.initials: BT
authors.lastname: Copeland
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bowman
authors.forename: Claude
authors.initials: C
authors.lastname: Boucheix
authors.forename: Leonie K
authors.initials: LK
authors.lastname: Ashman
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D055786:Gene Knockout Techniques; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D060245:Tetraspanin 29 / Q000235:genetics*
chemical_list: C554870:Cd9 protein, mouse; D060245:Tetraspanin 29
keywords: CD9; cancer; metastasis; prostate; tetraspanin