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ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer

Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency and are associated with lower overall survival in breast cancer compared to single cells. Combining single-cell RNA sequencing and protein analyses, here we report the profiles of primary tumor cells and lung metastases...

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Autores principales: Taftaf, Rokana, Liu, Xia, Singh, Salendra, Jia, Yuzhi, Dashzeveg, Nurmaa K., Hoffmann, Andrew D., El-Shennawy, Lamiaa, Ramos, Erika K., Adorno-Cruz, Valery, Schuster, Emma J., Scholten, David, Patel, Dhwani, Zhang, Youbin, Davis, Andrew A., Reduzzi, Carolina, Cao, Yue, D’Amico, Paolo, Shen, Yang, Cristofanilli, Massimo, Muller, William A., Varadan, Vinay, Liu, Huiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358026/
https://www.ncbi.nlm.nih.gov/pubmed/34381029
http://dx.doi.org/10.1038/s41467-021-25189-z
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author Taftaf, Rokana
Liu, Xia
Singh, Salendra
Jia, Yuzhi
Dashzeveg, Nurmaa K.
Hoffmann, Andrew D.
El-Shennawy, Lamiaa
Ramos, Erika K.
Adorno-Cruz, Valery
Schuster, Emma J.
Scholten, David
Patel, Dhwani
Zhang, Youbin
Davis, Andrew A.
Reduzzi, Carolina
Cao, Yue
D’Amico, Paolo
Shen, Yang
Cristofanilli, Massimo
Muller, William A.
Varadan, Vinay
Liu, Huiping
author_facet Taftaf, Rokana
Liu, Xia
Singh, Salendra
Jia, Yuzhi
Dashzeveg, Nurmaa K.
Hoffmann, Andrew D.
El-Shennawy, Lamiaa
Ramos, Erika K.
Adorno-Cruz, Valery
Schuster, Emma J.
Scholten, David
Patel, Dhwani
Zhang, Youbin
Davis, Andrew A.
Reduzzi, Carolina
Cao, Yue
D’Amico, Paolo
Shen, Yang
Cristofanilli, Massimo
Muller, William A.
Varadan, Vinay
Liu, Huiping
author_sort Taftaf, Rokana
collection PubMed
description Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency and are associated with lower overall survival in breast cancer compared to single cells. Combining single-cell RNA sequencing and protein analyses, here we report the profiles of primary tumor cells and lung metastases of triple-negative breast cancer (TNBC). ICAM1 expression increases by 200-fold in the lung metastases of three TNBC patient-derived xenografts (PDXs). Depletion of ICAM1 abrogates lung colonization of TNBC cells by inhibiting homotypic tumor cell-tumor cell cluster formation. Machine learning-based algorithms and mutagenesis analyses identify ICAM1 regions responsible for homophilic ICAM1-ICAM1 interactions, thereby directing homotypic tumor cell clustering, as well as heterotypic tumor-endothelial adhesion for trans-endothelial migration. Moreover, ICAM1 promotes metastasis by activating cellular pathways related to cell cycle and stemness. Finally, blocking ICAM1 interactions significantly inhibits CTC cluster formation, tumor cell transendothelial migration, and lung metastasis. Therefore, ICAM1 can serve as a novel therapeutic target for metastasis initiation of TNBC.
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spelling pubmed-83580262021-08-30 ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer Taftaf, Rokana Liu, Xia Singh, Salendra Jia, Yuzhi Dashzeveg, Nurmaa K. Hoffmann, Andrew D. El-Shennawy, Lamiaa Ramos, Erika K. Adorno-Cruz, Valery Schuster, Emma J. Scholten, David Patel, Dhwani Zhang, Youbin Davis, Andrew A. Reduzzi, Carolina Cao, Yue D’Amico, Paolo Shen, Yang Cristofanilli, Massimo Muller, William A. Varadan, Vinay Liu, Huiping Nat Commun Article Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency and are associated with lower overall survival in breast cancer compared to single cells. Combining single-cell RNA sequencing and protein analyses, here we report the profiles of primary tumor cells and lung metastases of triple-negative breast cancer (TNBC). ICAM1 expression increases by 200-fold in the lung metastases of three TNBC patient-derived xenografts (PDXs). Depletion of ICAM1 abrogates lung colonization of TNBC cells by inhibiting homotypic tumor cell-tumor cell cluster formation. Machine learning-based algorithms and mutagenesis analyses identify ICAM1 regions responsible for homophilic ICAM1-ICAM1 interactions, thereby directing homotypic tumor cell clustering, as well as heterotypic tumor-endothelial adhesion for trans-endothelial migration. Moreover, ICAM1 promotes metastasis by activating cellular pathways related to cell cycle and stemness. Finally, blocking ICAM1 interactions significantly inhibits CTC cluster formation, tumor cell transendothelial migration, and lung metastasis. Therefore, ICAM1 can serve as a novel therapeutic target for metastasis initiation of TNBC. Nature Publishing Group UK 2021-08-11 /pmc/articles/PMC8358026/ /pubmed/34381029 http://dx.doi.org/10.1038/s41467-021-25189-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Taftaf, Rokana
Liu, Xia
Singh, Salendra
Jia, Yuzhi
Dashzeveg, Nurmaa K.
Hoffmann, Andrew D.
El-Shennawy, Lamiaa
Ramos, Erika K.
Adorno-Cruz, Valery
Schuster, Emma J.
Scholten, David
Patel, Dhwani
Zhang, Youbin
Davis, Andrew A.
Reduzzi, Carolina
Cao, Yue
D’Amico, Paolo
Shen, Yang
Cristofanilli, Massimo
Muller, William A.
Varadan, Vinay
Liu, Huiping
ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer
title ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer
title_full ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer
title_fullStr ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer
title_full_unstemmed ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer
title_short ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer
title_sort icam1 initiates ctc cluster formation and trans-endothelial migration in lung metastasis of breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358026/
https://www.ncbi.nlm.nih.gov/pubmed/34381029
http://dx.doi.org/10.1038/s41467-021-25189-z
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