Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases
A dynamic interplay between prostate cancer (PCa) cells and reactive bone stroma modulates the growth of metastases within the bone microenvironment. Of the stromal cells, metastasis-associated fibroblasts (MAFs) are known to contribute but are the least studied cell type in PCa tumour progression....
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/6/861 |
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| author | Louisa C. E. Windus Nicholas Matigian Vicky M. Avery |
| author_facet | Louisa C. E. Windus Nicholas Matigian Vicky M. Avery |
| author_sort | Louisa C. E. Windus |
| collection | DOAJ |
| description | A dynamic interplay between prostate cancer (PCa) cells and reactive bone stroma modulates the growth of metastases within the bone microenvironment. Of the stromal cells, metastasis-associated fibroblasts (MAFs) are known to contribute but are the least studied cell type in PCa tumour progression. It is the aim of the current study to establish a biologically relevant 3D in vitro model that mimics the cellular and molecular profiles of MAFs found in vivo. Using 3D in vitro cell culture models, the bone-derived fibroblast cell line, HS-5, was treated with conditioned media from metastatic-derived PCa cell lines, PC3 and MDA-PCa 2b, or mouse-derived fibroblasts 3T3. Two corresponding reactive cell lines were propagated: HS5-PC3 and HS5-MDA, and evaluated for alterations in morphology, phenotype, cellular behaviour, plus protein and genomic profiles. HS5-PC3 and HS5-MDA displayed distinct alterations in expression levels of N-Cadherin, non-functional E-Cadherin, alpha-smooth muscle actin (α-SMA), Tenascin C, and vimentin, along with transforming growth factor receptor expression (TGF β R1 and R2), consistent with subpopulations of MAFs reported in vivo. Transcriptomic analysis revealed a reversion of HS5-PC3 towards a metastatic phenotype with an upregulation in pathways known to regulate cancer invasion, proliferation, and angiogenesis. The exploitation of these engineered 3D models could help further unravel the novel biology regulating metastatic growth and the role fibroblasts play in the colonisation process. |
| first_indexed | 2024-03-11T02:44:38Z |
| format | Article |
| id | doaj.art-4bd02fd516684d2da588315382123b2d |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T02:44:38Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-4bd02fd516684d2da588315382123b2d2023-11-18T09:23:34ZengMDPI AGBiology2079-77372023-06-0112686110.3390/biology12060861Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone MetastasesLouisa C. E. Windus0Nicholas Matigian1Vicky M. Avery2Discovery Biology, Centre for Cellular Phenomics, Griffith University, Nathan, QLD 4111, AustraliaQCIF Facility for Advanced Bioinformatics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, AustraliaDiscovery Biology, Centre for Cellular Phenomics, Griffith University, Nathan, QLD 4111, AustraliaA dynamic interplay between prostate cancer (PCa) cells and reactive bone stroma modulates the growth of metastases within the bone microenvironment. Of the stromal cells, metastasis-associated fibroblasts (MAFs) are known to contribute but are the least studied cell type in PCa tumour progression. It is the aim of the current study to establish a biologically relevant 3D in vitro model that mimics the cellular and molecular profiles of MAFs found in vivo. Using 3D in vitro cell culture models, the bone-derived fibroblast cell line, HS-5, was treated with conditioned media from metastatic-derived PCa cell lines, PC3 and MDA-PCa 2b, or mouse-derived fibroblasts 3T3. Two corresponding reactive cell lines were propagated: HS5-PC3 and HS5-MDA, and evaluated for alterations in morphology, phenotype, cellular behaviour, plus protein and genomic profiles. HS5-PC3 and HS5-MDA displayed distinct alterations in expression levels of N-Cadherin, non-functional E-Cadherin, alpha-smooth muscle actin (α-SMA), Tenascin C, and vimentin, along with transforming growth factor receptor expression (TGF β R1 and R2), consistent with subpopulations of MAFs reported in vivo. Transcriptomic analysis revealed a reversion of HS5-PC3 towards a metastatic phenotype with an upregulation in pathways known to regulate cancer invasion, proliferation, and angiogenesis. The exploitation of these engineered 3D models could help further unravel the novel biology regulating metastatic growth and the role fibroblasts play in the colonisation process.https://www.mdpi.com/2079-7737/12/6/861prostate cancertumour–stromal microenvironmentreactive bone stromal fibroblasts3D culturesEMT/MET |
| spellingShingle | Louisa C. E. Windus Nicholas Matigian Vicky M. Avery Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases Biology prostate cancer tumour–stromal microenvironment reactive bone stromal fibroblasts 3D cultures EMT/MET |
| title | Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases |
| title_full | Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases |
| title_fullStr | Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases |
| title_full_unstemmed | Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases |
| title_short | Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases |
| title_sort | induction of reactive bone stromal fibroblasts in 3d models of prostate cancer bone metastases |
| topic | prostate cancer tumour–stromal microenvironment reactive bone stromal fibroblasts 3D cultures EMT/MET |
| url | https://www.mdpi.com/2079-7737/12/6/861 |
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