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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 {alpha}6 integrin expression and an up-regulation of N-cadherin, Vimentin and {beta}1 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. -- Highlights: Black-Right-Pointing-Pointer We developedmore » and optimised 3D culturing techniques for Prostate Cancer cell-lines. Black-Right-Pointing-Pointer We investigated biomarker expression in 2D versus 3D culture techniques. Black-Right-Pointing-Pointer Metastatic PC3 cells re-expressed non-transcriptionally active androgen receptor. Black-Right-Pointing-Pointer Metastatic PCa cell lines retain in vivo-like antigenic profiles in 3D cultures.« less

Authors:
; ;  [1];  [1]
  1. Eskitis Institute for Cell and Molecular Therapies, Discovery Biology, Griffith University, Nathan 4111, Brisbane, Queensland (Australia)
Publication Date:
OSTI Identifier:
22212619
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 318; Journal Issue: 19; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANDROGENS; BIOLOGICAL MARKERS; CELL PROLIFERATION; DRUGS; IN VIVO; METASTASES; MORPHOLOGY; NEOPLASMS; PROSTATE; RECEPTORS

Citation Formats

Windus, Louisa C.E., Kiss, Debra L., Glover, Tristan, and Avery, Vicky M., E-mail: v.avery@griffith.edu.au. In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer. United States: N. p., 2012. Web. doi:10.1016/J.YEXCR.2012.07.013.
Windus, Louisa C.E., Kiss, Debra L., Glover, Tristan, & Avery, Vicky M., E-mail: v.avery@griffith.edu.au. In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer. United States. doi:10.1016/J.YEXCR.2012.07.013.
Windus, Louisa C.E., Kiss, Debra L., Glover, Tristan, and Avery, Vicky M., E-mail: v.avery@griffith.edu.au. Thu . "In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer". United States. doi:10.1016/J.YEXCR.2012.07.013.
@article{osti_22212619,
title = {In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer},
author = {Windus, Louisa C.E. and Kiss, Debra L. and Glover, Tristan and Avery, Vicky M., E-mail: v.avery@griffith.edu.au},
abstractNote = {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 {alpha}6 integrin expression and an up-regulation of N-cadherin, Vimentin and {beta}1 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. -- Highlights: Black-Right-Pointing-Pointer We developed and optimised 3D culturing techniques for Prostate Cancer cell-lines. Black-Right-Pointing-Pointer We investigated biomarker expression in 2D versus 3D culture techniques. Black-Right-Pointing-Pointer Metastatic PC3 cells re-expressed non-transcriptionally active androgen receptor. Black-Right-Pointing-Pointer Metastatic PCa cell lines retain in vivo-like antigenic profiles in 3D cultures.},
doi = {10.1016/J.YEXCR.2012.07.013},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 19,
volume = 318,
place = {United States},
year = {2012},
month = {11}
}