Endothelial cell-derived nidogen-1 inhibits migration of SK-BR-3 breast cancer cells.

Ferraro, D., Patella, F., Zanivan, S. R. , Donato, C., Aceto, N., Giannotta, M., Dejana, E., Diepenbruck, M., Christofori, G. and Buess, M. (2019) Endothelial cell-derived nidogen-1 inhibits migration of SK-BR-3 breast cancer cells. BMC Cancer, 19, 312. (doi: 10.1186/s12885-019-5521-8) (PMID:30947697) (PMCID:PMC6449935)

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Abstract

BACKGROUND: The tumour microenvironment is a critical regulator of malignant cancer progression. While endothelial cells have been widely studied in the context of tumour angiogenesis, their role as modulators of cancer cell invasion and migration is poorly understood. METHODS: We have investigated the influence of endothelial cells on the invasive and migratory behaviour of human cancer cells in vitro. RESULTS: Upon exposure to culture supernatants of endothelial cells, distinct cancer cells, such as SK-BR-3 cells, showed significantly increased invasion and cell migration concomitant with changes in cell morphology and gene expression reminiscent of an epithelial-mesenchymal transition (EMT). Interestingly, the pro-migratory effect on SK-BR-3 cells was significantly enhanced by supernatants obtained from subconfluent, proliferative endothelial cells rather than from confluent, quiescent endothelial cells. Systematically comparing the supernatants of subconfluent and confluent endothelial cells by quantitative MS proteomics revealed eight candidate proteins that were secreted at significantly higher levels by confluent endothelial cells representing potential inhibitors of cancer cell migration. Among these proteins, nidogen-1 was exclusively expressed in confluent endothelial cells and was found to be necessary and sufficient for the inhibition of SK-BR-3 cell migration. Indeed, SK-BR-3 cells exposed to nidogen-1-depleted endothelial supernatants showed increased promigratory STAT3 phosphorylation along with increased cell migration. This reflects the situation of enhanced SK-BR-3 migration upon stimulation with conditioned medium from subconfluent endothelial cells with inherent absence of nidogen-1 expression. CONCLUSION: The identification of nidogen-1 as an endothelial-derived inhibitor of migration of distinct cancer cell types reveals a novel mechanism of endothelial control over cancer progression.

Item Type:Articles
Additional Information:The study was supported be the Swiss National Science Foundation (Grant 3100030_135690/1 and 31003A_149940).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Zanivan, Professor Sara Rossana and Patella, Dr Francesca
Authors: Ferraro, D., Patella, F., Zanivan, S. R., Donato, C., Aceto, N., Giannotta, M., Dejana, E., Diepenbruck, M., Christofori, G., and Buess, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:BMC Cancer
Publisher:BioMed Central Ltd.
ISSN:1471-2407
ISSN (Online):1471-2407
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in BMC Cancer 19:312
Publisher Policy:Reproduced under a Creative Commons License

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