Cargando…

Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling

Metastasis requires tumour cells to cross endothelial cell (EC) barriers using pathways similar to those used by leucocytes during inflammation. Cell surface CD99 is expressed by healthy leucocytes and ECs, and participates in inflammatory transendothelial migration (TEM). Tumour cells also express...

Descripción completa

Detalles Bibliográficos
Autores principales: Mannion, Aarren J., Odell, Adam F., Taylor, Alison, Jones, Pamela F., Cook, Graham P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403985/
https://www.ncbi.nlm.nih.gov/pubmed/34374417
http://dx.doi.org/10.1242/jcs.240135
_version_ 1783746080704299008
author Mannion, Aarren J.
Odell, Adam F.
Taylor, Alison
Jones, Pamela F.
Cook, Graham P.
author_facet Mannion, Aarren J.
Odell, Adam F.
Taylor, Alison
Jones, Pamela F.
Cook, Graham P.
author_sort Mannion, Aarren J.
collection PubMed
description Metastasis requires tumour cells to cross endothelial cell (EC) barriers using pathways similar to those used by leucocytes during inflammation. Cell surface CD99 is expressed by healthy leucocytes and ECs, and participates in inflammatory transendothelial migration (TEM). Tumour cells also express CD99, and we have analysed its role in tumour progression and cancer cell TEM. Tumour cell CD99 was required for adhesion to ECs but inhibited invasion of the endothelial barrier and migratory activity. Furthermore, CD99 depletion in tumour cells caused redistribution of the actin cytoskeleton and increased activity of the Rho GTPase CDC42, known for its role in actin remodelling and cell migration. In a xenograft model of breast cancer, tumour cell CD99 expression inhibited metastatic progression, and patient samples showed reduced expression of the CD99 gene in brain metastases compared to matched primary breast tumours. We conclude that CD99 negatively regulates CDC42 and cell migration. However, CD99 has both pro- and anti-tumour activity, and our data suggest that this results in part from its functional linkage to CDC42 and the diverse signalling pathways downstream of this Rho GTPase. This article has an associated First Person interview with the first author of the paper.
format Online
Article
Text
id pubmed-8403985
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher The Company of Biologists Ltd
record_format MEDLINE/PubMed
spelling pubmed-84039852021-09-02 Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling Mannion, Aarren J. Odell, Adam F. Taylor, Alison Jones, Pamela F. Cook, Graham P. J Cell Sci Research Article Metastasis requires tumour cells to cross endothelial cell (EC) barriers using pathways similar to those used by leucocytes during inflammation. Cell surface CD99 is expressed by healthy leucocytes and ECs, and participates in inflammatory transendothelial migration (TEM). Tumour cells also express CD99, and we have analysed its role in tumour progression and cancer cell TEM. Tumour cell CD99 was required for adhesion to ECs but inhibited invasion of the endothelial barrier and migratory activity. Furthermore, CD99 depletion in tumour cells caused redistribution of the actin cytoskeleton and increased activity of the Rho GTPase CDC42, known for its role in actin remodelling and cell migration. In a xenograft model of breast cancer, tumour cell CD99 expression inhibited metastatic progression, and patient samples showed reduced expression of the CD99 gene in brain metastases compared to matched primary breast tumours. We conclude that CD99 negatively regulates CDC42 and cell migration. However, CD99 has both pro- and anti-tumour activity, and our data suggest that this results in part from its functional linkage to CDC42 and the diverse signalling pathways downstream of this Rho GTPase. This article has an associated First Person interview with the first author of the paper. The Company of Biologists Ltd 2021-08-10 /pmc/articles/PMC8403985/ /pubmed/34374417 http://dx.doi.org/10.1242/jcs.240135 Text en © 2021. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Mannion, Aarren J.
Odell, Adam F.
Taylor, Alison
Jones, Pamela F.
Cook, Graham P.
Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling
title Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling
title_full Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling
title_fullStr Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling
title_full_unstemmed Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling
title_short Tumour cell CD99 regulates transendothelial migration via CDC42 and actin remodelling
title_sort tumour cell cd99 regulates transendothelial migration via cdc42 and actin remodelling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403985/
https://www.ncbi.nlm.nih.gov/pubmed/34374417
http://dx.doi.org/10.1242/jcs.240135
work_keys_str_mv AT mannionaarrenj tumourcellcd99regulatestransendothelialmigrationviacdc42andactinremodelling
AT odelladamf tumourcellcd99regulatestransendothelialmigrationviacdc42andactinremodelling
AT tayloralison tumourcellcd99regulatestransendothelialmigrationviacdc42andactinremodelling
AT jonespamelaf tumourcellcd99regulatestransendothelialmigrationviacdc42andactinremodelling
AT cookgrahamp tumourcellcd99regulatestransendothelialmigrationviacdc42andactinremodelling