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Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells

Epithelial ovarian cancer metastasis is driven by spheroids, which are heterogeneous cancer cell aggregates released from the primary tumour mass that passively disseminate throughout the peritoneal cavity to promote tumour spread, disease recurrence, and acquired chemoresistance. Despite their clin...

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Detalles Bibliográficos
Autores principales: Bilandzic, Maree, Rainczuk, Adam, Green, Emma, Fairweather, Nicole, Jobling, Thomas W., Plebanski, Magdalena, Stephens, Andrew N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769856/
https://www.ncbi.nlm.nih.gov/pubmed/31443478
http://dx.doi.org/10.3390/cancers11091228
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author Bilandzic, Maree
Rainczuk, Adam
Green, Emma
Fairweather, Nicole
Jobling, Thomas W.
Plebanski, Magdalena
Stephens, Andrew N.
author_facet Bilandzic, Maree
Rainczuk, Adam
Green, Emma
Fairweather, Nicole
Jobling, Thomas W.
Plebanski, Magdalena
Stephens, Andrew N.
author_sort Bilandzic, Maree
collection PubMed
description Epithelial ovarian cancer metastasis is driven by spheroids, which are heterogeneous cancer cell aggregates released from the primary tumour mass that passively disseminate throughout the peritoneal cavity to promote tumour spread, disease recurrence, and acquired chemoresistance. Despite their clinical importance, the molecular events that control spheroid attachment and invasion into underlying healthy tissues remain poorly understood. We examined a novel in vitro invasion model using imaging mass spectrometry to establish a “snapshot” of the spheroid/mesothelial interface. Amongst numerous adhesion-related proteins, we identified a sub-population of highly motile, invasive cells that expressed the basal epithelial marker KRT14 as an absolute determinant of invasive potential. The loss of KRT14 completely abrogated the invasive capacity, but had no impact on cell viability or proliferation, suggesting an invasion-specific role. Our data demonstrate KRT14 cells as an ovarian cancer “leader cell” phenotype underlying tumor invasion, and suggest their importance as a clinically relevant target in directed anti-tumour therapies.
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spelling pubmed-67698562019-10-30 Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells Bilandzic, Maree Rainczuk, Adam Green, Emma Fairweather, Nicole Jobling, Thomas W. Plebanski, Magdalena Stephens, Andrew N. Cancers (Basel) Article Epithelial ovarian cancer metastasis is driven by spheroids, which are heterogeneous cancer cell aggregates released from the primary tumour mass that passively disseminate throughout the peritoneal cavity to promote tumour spread, disease recurrence, and acquired chemoresistance. Despite their clinical importance, the molecular events that control spheroid attachment and invasion into underlying healthy tissues remain poorly understood. We examined a novel in vitro invasion model using imaging mass spectrometry to establish a “snapshot” of the spheroid/mesothelial interface. Amongst numerous adhesion-related proteins, we identified a sub-population of highly motile, invasive cells that expressed the basal epithelial marker KRT14 as an absolute determinant of invasive potential. The loss of KRT14 completely abrogated the invasive capacity, but had no impact on cell viability or proliferation, suggesting an invasion-specific role. Our data demonstrate KRT14 cells as an ovarian cancer “leader cell” phenotype underlying tumor invasion, and suggest their importance as a clinically relevant target in directed anti-tumour therapies. MDPI 2019-08-22 /pmc/articles/PMC6769856/ /pubmed/31443478 http://dx.doi.org/10.3390/cancers11091228 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bilandzic, Maree
Rainczuk, Adam
Green, Emma
Fairweather, Nicole
Jobling, Thomas W.
Plebanski, Magdalena
Stephens, Andrew N.
Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells
title Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells
title_full Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells
title_fullStr Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells
title_full_unstemmed Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells
title_short Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells
title_sort keratin-14 (krt14) positive leader cells mediate mesothelial clearance and invasion by ovarian cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769856/
https://www.ncbi.nlm.nih.gov/pubmed/31443478
http://dx.doi.org/10.3390/cancers11091228
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