The endothelin system in breast tumour - endothelial cell interactions
The role of endothelin-1 (ET-1) and its receptors (ET-RA and ET-RB) in tumour development and progression involves complex interactions. ET-1, produced by tumours and associated cells like endothelial cells, functions in an autocrine and paracrine manner to promote tumour angiogenesis. Thus, we h...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Academy of Science of South Africa
2011-01-01
|
| Series: | South African Journal of Science |
| Subjects: | |
| Online Access: | https://www.sajs.co.za/article/view/10079 |
| _version_ | 1818443947221975040 |
|---|---|
| author | Tasnim Badat Julia Botha Strinivasen Naidoo |
| author_facet | Tasnim Badat Julia Botha Strinivasen Naidoo |
| author_sort | Tasnim Badat |
| collection | DOAJ |
| description | The role of endothelin-1 (ET-1) and its receptors (ET-RA and ET-RB) in tumour development and progression involves complex interactions. ET-1, produced by tumours and associated cells like endothelial cells, functions in an autocrine and paracrine manner to promote tumour angiogenesis. Thus, we hypothesised that endothelin, released into the tumour milieu by both tumours and the tumour vasculature, would influence angiogenesis. Therefore, this preliminary study aimed to investigate changes in ET1, ET-RA and ET-RB in breast tumour and microvascular endothelial cultures when each cell type was exposed directly to the other (co-culture model) as well as to the conditioned-medium metabolites of the other (challenge model). ET-1 secretion was measured by an enzyme-linked immunosorbent assay and ET-1, ET-RA and ET-RB expression investigated by the linked streptavidin - biotin method. In challenge experiments, endothelial metabolites significantly increased secretion of breast tumour ET-1. Tumour metabolites promoted endothelial membrane projections with no effect on ET-1 secretion. ET-1 and its receptors were immunolocalised in both cell types, including in projections. Increasing cancer cell conditioned medium resulted in decreased endothelial ET-RA and increased ET-RB staining. Co-cultures demonstrated ET proteins in projections of both cell types as well as at heterogeneous contact points. The findings support a role for the endothelin system in endothelial cell and breast cancer cell invasion. It is tempting to consider that early endothelial and tumour cell alterations may be promoted by ET-1 produced by both cell types. Further work is required that will examine localised cellular gene expression of the endothelin system as well as its pro-invasive and angiogenic effects in breast cancer models. |
| first_indexed | 2024-12-14T19:08:08Z |
| format | Article |
| id | doaj.art-968572e289d4484eae900eb1bf626c82 |
| institution | Directory Open Access Journal |
| issn | 1996-7489 |
| language | English |
| last_indexed | 2024-12-14T19:08:08Z |
| publishDate | 2011-01-01 |
| publisher | Academy of Science of South Africa |
| record_format | Article |
| series | South African Journal of Science |
| spelling | doaj.art-968572e289d4484eae900eb1bf626c822022-12-21T22:50:49ZengAcademy of Science of South AfricaSouth African Journal of Science1996-74892011-01-011071/2The endothelin system in breast tumour - endothelial cell interactionsTasnim Badat0Julia Botha1Strinivasen Naidoo2Department of Therapeutics and Medicines Management, University of KwaZulu- NatalDepartment of Therapeutics and Medicines Management, University of KwaZulu- NatalDepartment of Therapeutics and Medicines Management, University of KwaZulu- NatalThe role of endothelin-1 (ET-1) and its receptors (ET-RA and ET-RB) in tumour development and progression involves complex interactions. ET-1, produced by tumours and associated cells like endothelial cells, functions in an autocrine and paracrine manner to promote tumour angiogenesis. Thus, we hypothesised that endothelin, released into the tumour milieu by both tumours and the tumour vasculature, would influence angiogenesis. Therefore, this preliminary study aimed to investigate changes in ET1, ET-RA and ET-RB in breast tumour and microvascular endothelial cultures when each cell type was exposed directly to the other (co-culture model) as well as to the conditioned-medium metabolites of the other (challenge model). ET-1 secretion was measured by an enzyme-linked immunosorbent assay and ET-1, ET-RA and ET-RB expression investigated by the linked streptavidin - biotin method. In challenge experiments, endothelial metabolites significantly increased secretion of breast tumour ET-1. Tumour metabolites promoted endothelial membrane projections with no effect on ET-1 secretion. ET-1 and its receptors were immunolocalised in both cell types, including in projections. Increasing cancer cell conditioned medium resulted in decreased endothelial ET-RA and increased ET-RB staining. Co-cultures demonstrated ET proteins in projections of both cell types as well as at heterogeneous contact points. The findings support a role for the endothelin system in endothelial cell and breast cancer cell invasion. It is tempting to consider that early endothelial and tumour cell alterations may be promoted by ET-1 produced by both cell types. Further work is required that will examine localised cellular gene expression of the endothelin system as well as its pro-invasive and angiogenic effects in breast cancer models.https://www.sajs.co.za/article/view/10079CancerTumour-angiogenesisProtein systems |
| spellingShingle | Tasnim Badat Julia Botha Strinivasen Naidoo The endothelin system in breast tumour - endothelial cell interactions South African Journal of Science Cancer Tumour-angiogenesis Protein systems |
| title | The endothelin system in breast tumour - endothelial cell interactions |
| title_full | The endothelin system in breast tumour - endothelial cell interactions |
| title_fullStr | The endothelin system in breast tumour - endothelial cell interactions |
| title_full_unstemmed | The endothelin system in breast tumour - endothelial cell interactions |
| title_short | The endothelin system in breast tumour - endothelial cell interactions |
| title_sort | endothelin system in breast tumour endothelial cell interactions |
| topic | Cancer Tumour-angiogenesis Protein systems |
| url | https://www.sajs.co.za/article/view/10079 |
| work_keys_str_mv | AT tasnimbadat theendothelinsysteminbreasttumourendothelialcellinteractions AT juliabotha theendothelinsysteminbreasttumourendothelialcellinteractions AT strinivasennaidoo theendothelinsysteminbreasttumourendothelialcellinteractions AT tasnimbadat endothelinsysteminbreasttumourendothelialcellinteractions AT juliabotha endothelinsysteminbreasttumourendothelialcellinteractions AT strinivasennaidoo endothelinsysteminbreasttumourendothelialcellinteractions |