title: In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer.
abstract: Here we report that Prostate Cancer (PCa) cell-lines DU145, PC3, LNCaP and RWPE-1 grown in 3D matrices in contrast to conventional 2D monolayers, display distinct differences in cell morphology, proliferation and expression of important biomarker proteins associated with cancer progression. Consistent with in vivo growth rates, in 3D cultures, all PCa cell-lines were found to proliferate at significantly lower rates in comparison to their 2D counterparts. Moreover, when grown in a 3D matrix, metastatic PC3 cell-lines were found to mimic more precisely protein expression patterns of metastatic tumour formation as found in vivo. In comparison to the prostate epithelial cell-line RWPE-1, metastatic PC3 cell-lines exhibited a down-regulation of E-cadherin and α6 integrin expression and an up-regulation of N-cadherin, Vimentin and β1 integrin expression and re-expressed non-transcriptionally active AR. In comparison to the non-invasive LNCaP cell-lines, PC3 cells were found to have an up-regulation of chemokine receptor CXCR4, consistent with a metastatic phenotype. In 2D cultures, there was little distinction in protein expression between metastatic, non-invasive and epithelial cells. These results suggest that 3D cultures are more representative of in vivo morphology and may serve as a more biologically relevant model in the drug discovery pipeline.
authors: Eskitis Institute for Cell and Molecular Therapies, Discovery Biology, Griffith University, Nathan 4111, Brisbane, Queensland, Australia.
authors: Louisa C E
authors: LC
authors: Windus
authors: Debra L
authors: DL
authors: Kiss
authors: Tristan
authors: T
authors: Glover
authors: Vicky M
authors: VM
authors: Avery
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D015820:Cadherins; D039503:Integrin alpha6; D019012:Integrin beta1; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D014746:Vimentin; D019061:src-Family Kinases