The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer

Understanding how heterogeneous cancer cell populations migrate collectively is of paramount importance to arrest metastasis. Here, we applied 3D culture-based approaches for in vitro modeling of the collective migration of squamous carcinoma cells and examine the impact of epithelial and mesenchyma...

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Main Authors: Inés Saénz-de-Santa-María, Lucía Celada, María-Dolores Chiara
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/9/3/731
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author Inés Saénz-de-Santa-María
Lucía Celada
María-Dolores Chiara
author_facet Inés Saénz-de-Santa-María
Lucía Celada
María-Dolores Chiara
author_sort Inés Saénz-de-Santa-María
collection DOAJ
description Understanding how heterogeneous cancer cell populations migrate collectively is of paramount importance to arrest metastasis. Here, we applied 3D culture-based approaches for in vitro modeling of the collective migration of squamous carcinoma cells and examine the impact of epithelial and mesenchymal cell interactions on this type of migration. We show that both mesenchymal N-cadherin-expressing cancer cells and cancer-associated fibroblasts cooperate in collective migration of epithelial cancer cells by leading their collective migration. This was consistent with the observed distribution of E-cadherin/N-cadherin in the human carcinoma tissues of head and neck. The presence of “leader” mesenchymal cancer cells or “leader” fibroblasts was significantly associated with metastasis development, recurrent disease and low overall disease survival in head and neck squamous cell carcinomas (HNSCC). In silico analysis of independent public datasets revealed that increased N-cadherin expression in the heterogeneous cancer tissues is associated with disease progression not only in HNSCC but also in other prevalent tumors, such as colorectal, breast and lung cancer. Collectively, our data highlight the importance of mesenchymal cells in collective cell migration and disease progression, findings that may have a broad significance in cancer, especially in those in which aberrant N-cadherin expression negatively impacts disease survival.
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spelling doaj.art-767acf00e3974eadbfa9e448fe13e45f2023-09-02T09:15:47ZengMDPI AGCells2073-44092020-03-019373110.3390/cells9030731cells9030731The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial CancerInés Saénz-de-Santa-María0Lucía Celada1María-Dolores Chiara2Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainInstituto de Investigación Sanitaria del Principado de Asturias, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainInstituto de Investigación Sanitaria del Principado de Asturias, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainUnderstanding how heterogeneous cancer cell populations migrate collectively is of paramount importance to arrest metastasis. Here, we applied 3D culture-based approaches for in vitro modeling of the collective migration of squamous carcinoma cells and examine the impact of epithelial and mesenchymal cell interactions on this type of migration. We show that both mesenchymal N-cadherin-expressing cancer cells and cancer-associated fibroblasts cooperate in collective migration of epithelial cancer cells by leading their collective migration. This was consistent with the observed distribution of E-cadherin/N-cadherin in the human carcinoma tissues of head and neck. The presence of “leader” mesenchymal cancer cells or “leader” fibroblasts was significantly associated with metastasis development, recurrent disease and low overall disease survival in head and neck squamous cell carcinomas (HNSCC). In silico analysis of independent public datasets revealed that increased N-cadherin expression in the heterogeneous cancer tissues is associated with disease progression not only in HNSCC but also in other prevalent tumors, such as colorectal, breast and lung cancer. Collectively, our data highlight the importance of mesenchymal cells in collective cell migration and disease progression, findings that may have a broad significance in cancer, especially in those in which aberrant N-cadherin expression negatively impacts disease survival.https://www.mdpi.com/2073-4409/9/3/731collective cell migrationn-cadherine-cadherinepithelia–mesenchymal transitioncancer-associated fibroblasts
spellingShingle Inés Saénz-de-Santa-María
Lucía Celada
María-Dolores Chiara
The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer
Cells
collective cell migration
n-cadherin
e-cadherin
epithelia–mesenchymal transition
cancer-associated fibroblasts
title The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer
title_full The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer
title_fullStr The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer
title_full_unstemmed The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer
title_short The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer
title_sort leader position of mesenchymal cells expressing n cadherin in the collective migration of epithelial cancer
topic collective cell migration
n-cadherin
e-cadherin
epithelia–mesenchymal transition
cancer-associated fibroblasts
url https://www.mdpi.com/2073-4409/9/3/731
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