ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling.
The neurotrophic factor ARTEMIN (ARTN) has been reported to possess a role in mammary carcinoma progression and metastasis. Herein, we report that ARTN modulates endothelial cell behaviour and promotes angiogenesis in ER-mammary carcinoma (ER-MC). Human microvascular endothelial cells (HMEC-1) do no...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3503764?pdf=render |
| _version_ | 1818511149215252480 |
|---|---|
| author | Arindam Banerjee Zheng-Sheng Wu Peng-Xu Qian Jian Kang Dong-Xu Liu Tao Zhu Peter E Lobie |
| author_facet | Arindam Banerjee Zheng-Sheng Wu Peng-Xu Qian Jian Kang Dong-Xu Liu Tao Zhu Peter E Lobie |
| author_sort | Arindam Banerjee |
| collection | DOAJ |
| description | The neurotrophic factor ARTEMIN (ARTN) has been reported to possess a role in mammary carcinoma progression and metastasis. Herein, we report that ARTN modulates endothelial cell behaviour and promotes angiogenesis in ER-mammary carcinoma (ER-MC). Human microvascular endothelial cells (HMEC-1) do not express ARTN but respond to exogenously added, and paracrine ARTN secreted by ER-MC cells. ARTN promoted endothelial cell proliferation, migration, invasion and 3D matrigel tube formation. Angiogenic behaviour promoted by ARTN secreted by ER-MC cells was mediated by AKT with resultant increased TWIST1 and subsequently VEGF-A expression. In a patient cohort of ER-MC, ARTN positively correlated with VEGF-A expression as measured by Spearman's rank correlation analysis. In xenograft experiments, ER-MC cells with forced expression of ARTN produced tumors with increased VEGF-A expression and increased microvessel density (CD31 and CD34) compared to tumors formed by control cells. Functional inhibition of ARTN by siRNA decreased the angiogenic effects of ER-MC cells. Bevacizumab (a humanized monoclonal anti-VEGF-A antibody) partially inhibited the ARTN mediated angiogenic effects of ER-MC cells and combined inhibition of ARTN and VEGF-A by the same resulted in further significant decrease in the angiogenic effects of ER-MC cells. Thus, ARTN stimulates de novo tumor angiogenesis mediated in part by VEGF-A. ARTN therefore co-ordinately regulates multiple aspects of tumor growth and metastasis. |
| first_indexed | 2024-12-10T23:29:31Z |
| format | Article |
| id | doaj.art-093ee0b403614462b5c98fa673ddbb3a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T23:29:31Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-093ee0b403614462b5c98fa673ddbb3a2022-12-22T01:29:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5009810.1371/journal.pone.0050098ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling.Arindam BanerjeeZheng-Sheng WuPeng-Xu QianJian KangDong-Xu LiuTao ZhuPeter E LobieThe neurotrophic factor ARTEMIN (ARTN) has been reported to possess a role in mammary carcinoma progression and metastasis. Herein, we report that ARTN modulates endothelial cell behaviour and promotes angiogenesis in ER-mammary carcinoma (ER-MC). Human microvascular endothelial cells (HMEC-1) do not express ARTN but respond to exogenously added, and paracrine ARTN secreted by ER-MC cells. ARTN promoted endothelial cell proliferation, migration, invasion and 3D matrigel tube formation. Angiogenic behaviour promoted by ARTN secreted by ER-MC cells was mediated by AKT with resultant increased TWIST1 and subsequently VEGF-A expression. In a patient cohort of ER-MC, ARTN positively correlated with VEGF-A expression as measured by Spearman's rank correlation analysis. In xenograft experiments, ER-MC cells with forced expression of ARTN produced tumors with increased VEGF-A expression and increased microvessel density (CD31 and CD34) compared to tumors formed by control cells. Functional inhibition of ARTN by siRNA decreased the angiogenic effects of ER-MC cells. Bevacizumab (a humanized monoclonal anti-VEGF-A antibody) partially inhibited the ARTN mediated angiogenic effects of ER-MC cells and combined inhibition of ARTN and VEGF-A by the same resulted in further significant decrease in the angiogenic effects of ER-MC cells. Thus, ARTN stimulates de novo tumor angiogenesis mediated in part by VEGF-A. ARTN therefore co-ordinately regulates multiple aspects of tumor growth and metastasis.http://europepmc.org/articles/PMC3503764?pdf=render |
| spellingShingle | Arindam Banerjee Zheng-Sheng Wu Peng-Xu Qian Jian Kang Dong-Xu Liu Tao Zhu Peter E Lobie ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling. PLoS ONE |
| title | ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling. |
| title_full | ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling. |
| title_fullStr | ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling. |
| title_full_unstemmed | ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling. |
| title_short | ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling. |
| title_sort | artemin promotes de novo angiogenesis in er negative mammary carcinoma through activation of twist1 vegf a signalling |
| url | http://europepmc.org/articles/PMC3503764?pdf=render |
| work_keys_str_mv | AT arindambanerjee arteminpromotesdenovoangiogenesisinernegativemammarycarcinomathroughactivationoftwist1vegfasignalling AT zhengshengwu arteminpromotesdenovoangiogenesisinernegativemammarycarcinomathroughactivationoftwist1vegfasignalling AT pengxuqian arteminpromotesdenovoangiogenesisinernegativemammarycarcinomathroughactivationoftwist1vegfasignalling AT jiankang arteminpromotesdenovoangiogenesisinernegativemammarycarcinomathroughactivationoftwist1vegfasignalling AT dongxuliu arteminpromotesdenovoangiogenesisinernegativemammarycarcinomathroughactivationoftwist1vegfasignalling AT taozhu arteminpromotesdenovoangiogenesisinernegativemammarycarcinomathroughactivationoftwist1vegfasignalling AT peterelobie arteminpromotesdenovoangiogenesisinernegativemammarycarcinomathroughactivationoftwist1vegfasignalling |