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Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation

Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasiv...

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Autores principales: Pekkonen, Pirita, Alve, Sanni, Balistreri, Giuseppe, Gramolelli, Silvia, Tatti-Bugaeva, Olga, Paatero, Ilkka, Niiranen, Otso, Tuohinto, Krista, Perälä, Nina, Taiwo, Adewale, Zinovkina, Nadezhda, Repo, Pauliina, Icay, Katherine, Ivaska, Johanna, Saharinen, Pipsa, Hautaniemi, Sampsa, Lehti, Kaisa, Ojala, Päivi M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929907/
https://www.ncbi.nlm.nih.gov/pubmed/29712618
http://dx.doi.org/10.7554/eLife.32490
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author Pekkonen, Pirita
Alve, Sanni
Balistreri, Giuseppe
Gramolelli, Silvia
Tatti-Bugaeva, Olga
Paatero, Ilkka
Niiranen, Otso
Tuohinto, Krista
Perälä, Nina
Taiwo, Adewale
Zinovkina, Nadezhda
Repo, Pauliina
Icay, Katherine
Ivaska, Johanna
Saharinen, Pipsa
Hautaniemi, Sampsa
Lehti, Kaisa
Ojala, Päivi M
author_facet Pekkonen, Pirita
Alve, Sanni
Balistreri, Giuseppe
Gramolelli, Silvia
Tatti-Bugaeva, Olga
Paatero, Ilkka
Niiranen, Otso
Tuohinto, Krista
Perälä, Nina
Taiwo, Adewale
Zinovkina, Nadezhda
Repo, Pauliina
Icay, Katherine
Ivaska, Johanna
Saharinen, Pipsa
Hautaniemi, Sampsa
Lehti, Kaisa
Ojala, Päivi M
author_sort Pekkonen, Pirita
collection PubMed
description Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and β1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident β1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype.
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spelling pubmed-59299072018-05-03 Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation Pekkonen, Pirita Alve, Sanni Balistreri, Giuseppe Gramolelli, Silvia Tatti-Bugaeva, Olga Paatero, Ilkka Niiranen, Otso Tuohinto, Krista Perälä, Nina Taiwo, Adewale Zinovkina, Nadezhda Repo, Pauliina Icay, Katherine Ivaska, Johanna Saharinen, Pipsa Hautaniemi, Sampsa Lehti, Kaisa Ojala, Päivi M eLife Cancer Biology Lymphatic invasion and lymph node metastasis correlate with poor clinical outcome in melanoma. However, the mechanisms of lymphatic dissemination in distant metastasis remain incompletely understood. We show here that exposure of expansively growing human WM852 melanoma cells, but not singly invasive Bowes cells, to lymphatic endothelial cells (LEC) in 3D co-culture facilitates melanoma distant organ metastasis in mice. To dissect the underlying molecular mechanisms, we established LEC co-cultures with different melanoma cells originating from primary tumors or metastases. Notably, the expansively growing metastatic melanoma cells adopted an invasively sprouting phenotype in 3D matrix that was dependent on MMP14, Notch3 and β1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident β1-integrin activation. Moreover, MMP14 and Notch3 were required for LEC-mediated metastasis of zebrafish xenografts. This study uncovers a unique mechanism whereby LEC contact promotes melanoma metastasis by inducing a reversible switch from 3D growth to invasively sprouting cell phenotype. eLife Sciences Publications, Ltd 2018-05-01 /pmc/articles/PMC5929907/ /pubmed/29712618 http://dx.doi.org/10.7554/eLife.32490 Text en © 2018, Pekkonen et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Pekkonen, Pirita
Alve, Sanni
Balistreri, Giuseppe
Gramolelli, Silvia
Tatti-Bugaeva, Olga
Paatero, Ilkka
Niiranen, Otso
Tuohinto, Krista
Perälä, Nina
Taiwo, Adewale
Zinovkina, Nadezhda
Repo, Pauliina
Icay, Katherine
Ivaska, Johanna
Saharinen, Pipsa
Hautaniemi, Sampsa
Lehti, Kaisa
Ojala, Päivi M
Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation
title Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation
title_full Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation
title_fullStr Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation
title_full_unstemmed Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation
title_short Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation
title_sort lymphatic endothelium stimulates melanoma metastasis and invasion via mmp14-dependent notch3 and β1-integrin activation
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929907/
https://www.ncbi.nlm.nih.gov/pubmed/29712618
http://dx.doi.org/10.7554/eLife.32490
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