The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines
Tumours exhibit a heterogeneous mix of cell types that reciprocally regulate their growth in the tumour stroma, considerably affecting the progression of the disease. Both adipose-derived mesenchymal stem cells and Wnt signalling pathway are vital in driving breast tumour growth. Hence, we examined...
| Main Authors: | , , , , |
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| Format: | Journal Article |
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Pergamon
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/60555 |
| _version_ | 1848760615956381696 |
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| author | Visweswaran, M. Arfuso, Frank Dilley, R. Newsholme, P. Dharmarajan, Arunasalam |
| author_facet | Visweswaran, M. Arfuso, Frank Dilley, R. Newsholme, P. Dharmarajan, Arunasalam |
| author_sort | Visweswaran, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Tumours exhibit a heterogeneous mix of cell types that reciprocally regulate their growth in the tumour stroma, considerably affecting the progression of the disease. Both adipose-derived mesenchymal stem cells and Wnt signalling pathway are vital in driving breast tumour growth. Hence, we examined the effect of secreted factors released by adipose-derived mesenchymal stem cells, and further explored the anti-tumour property of the Wnt antagonist secreted frizzled-related protein 4 (sFRP4) on MCF-7 and MDA-MB-231 breast tumour cells. We observed that conditioned medium and extracellular matrix derived from adipose-derived mesenchymal stem cells inhibited tumour viability. The inhibitory effect of the conditioned medium was retained within its low molecular weight and non-protein component. The conditioned medium also induced apoptosis accompanied by a decrease in the mitochondrial membrane potential in tumour cells, Furthermore, it downregulated the protein expression of active ß-catenin and Cyclin D1, which are major target proteins of the Wnt signalling pathway, and reduced the expression of anti-apoptotic protein Bcl-xL. The combination of conditioned medium and sFRP4 further potentiated the effects, depending on the tumour cell line and experimental assay. We conclude that factors derived from conditioned medium of adipose-derived mesenchymal stem cells and sFRP4 significantly decreased the tumour cell viability and migration rates (MCF-7), accompanied with an enhanced apoptotic activity through inhibition of canonical Wnt signalling. Besides giving an insight to possible paracrine interactions and influence of signalling pathways, reflective of a breast tumour microenvironment, this study emphasises the utilization of cell free-secreted factors and Wnt antagonists to improve conventional anti-cancer strategies. |
| first_indexed | 2025-11-14T10:18:36Z |
| format | Journal Article |
| id | curtin-20.500.11937-60555 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:18:36Z |
| publishDate | 2017 |
| publisher | Pergamon |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-605552019-01-10T07:49:04Z The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines Visweswaran, M. Arfuso, Frank Dilley, R. Newsholme, P. Dharmarajan, Arunasalam Tumours exhibit a heterogeneous mix of cell types that reciprocally regulate their growth in the tumour stroma, considerably affecting the progression of the disease. Both adipose-derived mesenchymal stem cells and Wnt signalling pathway are vital in driving breast tumour growth. Hence, we examined the effect of secreted factors released by adipose-derived mesenchymal stem cells, and further explored the anti-tumour property of the Wnt antagonist secreted frizzled-related protein 4 (sFRP4) on MCF-7 and MDA-MB-231 breast tumour cells. We observed that conditioned medium and extracellular matrix derived from adipose-derived mesenchymal stem cells inhibited tumour viability. The inhibitory effect of the conditioned medium was retained within its low molecular weight and non-protein component. The conditioned medium also induced apoptosis accompanied by a decrease in the mitochondrial membrane potential in tumour cells, Furthermore, it downregulated the protein expression of active ß-catenin and Cyclin D1, which are major target proteins of the Wnt signalling pathway, and reduced the expression of anti-apoptotic protein Bcl-xL. The combination of conditioned medium and sFRP4 further potentiated the effects, depending on the tumour cell line and experimental assay. We conclude that factors derived from conditioned medium of adipose-derived mesenchymal stem cells and sFRP4 significantly decreased the tumour cell viability and migration rates (MCF-7), accompanied with an enhanced apoptotic activity through inhibition of canonical Wnt signalling. Besides giving an insight to possible paracrine interactions and influence of signalling pathways, reflective of a breast tumour microenvironment, this study emphasises the utilization of cell free-secreted factors and Wnt antagonists to improve conventional anti-cancer strategies. 2017 Journal Article http://hdl.handle.net/20.500.11937/60555 10.1016/j.biocel.2017.12.013 Pergamon fulltext |
| spellingShingle | Visweswaran, M. Arfuso, Frank Dilley, R. Newsholme, P. Dharmarajan, Arunasalam The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines |
| title | The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines |
| title_full | The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines |
| title_fullStr | The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines |
| title_full_unstemmed | The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines |
| title_short | The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines |
| title_sort | inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and wnt antagonism on breast tumour cell lines |
| url | http://hdl.handle.net/20.500.11937/60555 |