Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer

Windus, Louisa C. E. and Glover, Tristan T. and Avery, Vicky M. (2013) Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer. Molecular Cancer, 12:112. pp. 1-19.

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The cellular and molecular mechanisms that mediate interactions between tumour cells and the surrounding bone stroma are to date largely undetermined in prostate cancer (PCa) progression. The purpose of this study was to evaluate the role of alpha 6 and beta 1 integrin subunits in mediating tumour-stromal interactions.

Utilising 3D in vitro assays we evaluated and compared 1. Monocultures of prostate metastatic PC3, bone stromal derived HS5 and prostate epithelial RWPE-1 cells and 2. Tumour-stromal co-cultures (PC3 + HS5) to ascertain changes in cellular phenotype, function and expression of metastatic markers.

In comparison to 3D monocultures of PC3 or HS5 cells, when cultured together, these cells displayed up-regulated invasive and proliferative qualities, along with altered expression of epithelial-to-mesenchymal and chemokine protein constituents implicated in metastatic dissemination. When co-cultured, HS5 cells were found to re-express N-Cadherin and chemokine receptor CXCR7. Alterations in N-Cadherin expression were found to be mediated by soluble factors secreted by PC3 tumour cells, while chemokine receptor re-expression was dependent on direct cell-cell interactions. We have also shown that integrins beta 1 and alpha 6 play an integral role in maintaining cell homeostasis and mediating expression of E-Cadherin, N-Cadherin and vimentin, in addition to chemokine receptor CXCR7.

Collectively our results suggest that both PC3 and HS5 cells provide a 'protective' and reciprocal milieu that promotes tumour growth. As such 3D co-cultures may serve as a more complex and valid biological model in the drug discovery pipeline.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: No Faculty
Faculty/School / Institute/Centre: No Faculty
Date Deposited: 27 Oct 2020 03:00
Last Modified: 27 Oct 2020 05:28
Uncontrolled Keywords: Prostate cancer, Tumour-stromal microenvironment, 3D co-cultures, EMT markers, Chemokine CXCR7, Integrins
Fields of Research (2008): 06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060103 Cell Development, Proliferation and Death
Socio-Economic Objectives (2008): E Expanding Knowledge > 97 Expanding Knowledge > 970106 Expanding Knowledge in the Biological Sciences
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