Angiotensin II facilitates breast cancer cell migration and metastasis.
Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated wheth...
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2012
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oai:doaj.org-article:080dd26831f04bd1855e2d4ec677f9ea2021-11-18T07:21:24ZAngiotensin II facilitates breast cancer cell migration and metastasis.1932-620310.1371/journal.pone.0035667https://doaj.org/article/080dd26831f04bd1855e2d4ec677f9ea2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22536420/?tool=EBIhttps://doaj.org/toc/1932-6203Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors.Sylvie Rodrigues-FerreiraMohamed AbdelkarimPatricia Dillenburg-PillaAnny-Claude LuissintAnne di-TommasoFrédérique DeshayesCarmen Lucia S PontesAngie MolinaNicolas CagnardFranck LetourneurMarina MorelRosana I ReisDulce E CasariniBenoit TerrisPierre-Olivier CouraudClaudio M Costa-NetoMélanie Di BenedettoClara NahmiasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35667 (2012) |
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| collection |
DOAJ |
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EN |
| topic |
Medicine R Science Q |
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Medicine R Science Q Sylvie Rodrigues-Ferreira Mohamed Abdelkarim Patricia Dillenburg-Pilla Anny-Claude Luissint Anne di-Tommaso Frédérique Deshayes Carmen Lucia S Pontes Angie Molina Nicolas Cagnard Franck Letourneur Marina Morel Rosana I Reis Dulce E Casarini Benoit Terris Pierre-Olivier Couraud Claudio M Costa-Neto Mélanie Di Benedetto Clara Nahmias Angiotensin II facilitates breast cancer cell migration and metastasis. |
| description |
Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors. |
| format |
article |
| author |
Sylvie Rodrigues-Ferreira Mohamed Abdelkarim Patricia Dillenburg-Pilla Anny-Claude Luissint Anne di-Tommaso Frédérique Deshayes Carmen Lucia S Pontes Angie Molina Nicolas Cagnard Franck Letourneur Marina Morel Rosana I Reis Dulce E Casarini Benoit Terris Pierre-Olivier Couraud Claudio M Costa-Neto Mélanie Di Benedetto Clara Nahmias |
| author_facet |
Sylvie Rodrigues-Ferreira Mohamed Abdelkarim Patricia Dillenburg-Pilla Anny-Claude Luissint Anne di-Tommaso Frédérique Deshayes Carmen Lucia S Pontes Angie Molina Nicolas Cagnard Franck Letourneur Marina Morel Rosana I Reis Dulce E Casarini Benoit Terris Pierre-Olivier Couraud Claudio M Costa-Neto Mélanie Di Benedetto Clara Nahmias |
| author_sort |
Sylvie Rodrigues-Ferreira |
| title |
Angiotensin II facilitates breast cancer cell migration and metastasis. |
| title_short |
Angiotensin II facilitates breast cancer cell migration and metastasis. |
| title_full |
Angiotensin II facilitates breast cancer cell migration and metastasis. |
| title_fullStr |
Angiotensin II facilitates breast cancer cell migration and metastasis. |
| title_full_unstemmed |
Angiotensin II facilitates breast cancer cell migration and metastasis. |
| title_sort |
angiotensin ii facilitates breast cancer cell migration and metastasis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/080dd26831f04bd1855e2d4ec677f9ea |
| work_keys_str_mv |
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