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- W1557531372 abstract "Proc Amer Assoc Cancer Res, Volume 47, 20065151 Growth of prostate epithelial cells in three-dimensional (3D) culture allows cells to form structures that more closely resemble their in vivo architecture. This permits further investigation into signaling pathways that control tumorigenesis in a biologically relevant context. In this study our objective was to assess whether the 3D assay (Petersen et al.1992) recapitulates the growth characteristics of human prostate epithelial cell lines in vivo . We used three human prostate epithelial cell lines, all derived from the same lineage: P69, an SV40 large T antigen immortalized human nonmalignant epithelial cell line that is non-tumorigenic; M12, a highly tumorigenic and metastatic subline derived from the P69 line, which displays a novel 16;19 chromosomal translocation resulting in the deletion of one copy of 19p-q13.1; and M12(F6), a slow growing, poorly tumorigenic subline created from M12 by the stable re-introduction of an intact human chromosome 19. The non-tumorigenic P69 line, when grown in Matrigel, organized into spheroids, commonly called acini, with a clearly defined lumen. Moreover, immunostaining with antibodies to α6- and β1-integrins showed polarization typical of glandular epithelium. The tumorigenic and metastatic M12 subline developed into highly disorganized clusters of cells exhibiting no polarization. The M12(F6) subline, which was converted to a slow growing and poorly tumorigenic line by the re-introduction of chromosome 19, reverted to forming acini-like structures with limited polarity. In the presence of the β1-integrin inhibitory antibody, AIIB2, M12 cells also reverted to forming acini. These findings indicate that growth in 3D culture closely parallels the phenotype of these prostate cells as observed in vivo in athymic nude mice, i.e., the inability to form organized acini with polarized epithelial structure in 3D parallels tumorigenicity. Moreover, β1-integrin must play a key role in acini formation as has been shown previously for the breast cells in 3D cultures (Weaver et al.1977).. These results suggest a highly relevant model system for further investigation of cancer genes and signaling pathways important to tumorigenesis and/or metastasis. This work was supported in part by DOD grant PC040763 to ZEZ and by funding from the DOE, NIH and DOD to MJB." @default.
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- W1557531372 date "2006-04-15" @default.
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- W1557531372 title "Modeling prostate epithelial cancer cells in three-dimensional cultures in Matrigel." @default.
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