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Open AccessArticle

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

1
Instituto de Investigación Sanitaria del Principado de Asturias, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain
2
CIBERONC, 28029 Madrid, Spain
3
Instituto de Oncología del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain
*
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 731; https://doi.org/10.3390/cells9030731
Received: 31 January 2020 / Revised: 11 March 2020 / Accepted: 11 March 2020 / Published: 16 March 2020
(This article belongs to the Section Cell Motility and Adhesion)
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. View Full-Text
Keywords: collective cell migration; N-cadherin; E-cadherin; epithelia–mesenchymal transition; cancer-associated fibroblasts collective cell migration; N-cadherin; E-cadherin; epithelia–mesenchymal transition; cancer-associated fibroblasts
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Saénz-de-Santa-María, I.; Celada, L.; Chiara, M.-D. The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer. Cells 2020, 9, 731.

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