Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and beta 1-integrin activation
Krista Tuohinto; Sampsa Hautaniemi; Pirita Pekkonen; Adewale Taiwo; Katherine Icay; Ilkka Paatero; Silvia Gramolelli; Pipsa Saharinen; Otso Niiranen; Nina Perälä; Pauliina Repo; Nadezhda Zinovkina; Johanna Ivaska; Sanni Alve; Olga Tatti-Bugaeva; Giuseppe Balistreri; Kaisa Lehti; Päivi M Ojala
Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and beta 1-integrin activation
Krista Tuohinto
Sampsa Hautaniemi
Pirita Pekkonen
Adewale Taiwo
Katherine Icay
Ilkka Paatero
Silvia Gramolelli
Pipsa Saharinen
Otso Niiranen
Nina Perälä
Pauliina Repo
Nadezhda Zinovkina
Johanna Ivaska
Sanni Alve
Olga Tatti-Bugaeva
Giuseppe Balistreri
Kaisa Lehti
Päivi M Ojala
ELIFE SCIENCES PUBLICATIONS LTD
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042719253
https://urn.fi/URN:NBN:fi-fe2021042719253
Tiivistelmä
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 beta 1-integrin. Unexpectedly, MMP14 was necessary for LEC-induced Notch3 induction and coincident beta 1-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.
Kokoelmat
- Rinnakkaistallenteet [19207]