Macrophage-dependent tumor cell transendothelial migration is mediated by Notch1/Mena INV-initiated invadopodium formation
Jeanine Pignatelli,Jose Javier Bravo-Cordero,Minna Roh-Johnson,Minna Roh-Johnson,Saumil J. Gandhi,Yarong Wang,Xiaoming Chen,Robert J. Eddy,Alice Xue,Robert H. Singer,Louis Hodgson,Maja H. Oktay,John S. Condeelis +12 more
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TLDR
A novel role for Notch1 signaling in the regulation of MenaINV expression and transendothelial migration is indicated and mechanistic information essential to the use of therapeutic inhibitors of metastasis is provided.Abstract:
The process of intravasation involving transendothelial migration is a key step in metastatic spread. How the triple cell complex composed of a macrophage, Mena over-expressing tumor cell and endothelial cell, called the tumor microenvironment of metastasis (TMEM), facilitates tumor cell transendothelial migration is not completely understood. Previous work has shown that the physical contact between a macrophage and tumor cell results in the formation of invadopodia, actin-rich matrix degrading protrusions, important for tumor cell invasion and transendothelial migration and tumor cell dissemination. Herein, we show that the macrophage-induced invadopodium is formed through a Notch1/MenaINV signaling pathway in the tumor cell upon macrophage contact. This heterotypic tumor cell - macrophage interaction results in the upregulation of MenaINV through the activation of MENA transcription. Notch1 and MenaINV expression are required for tumor cell transendothelial migration, a necessary step during intravasation. Inhibition of the Notch signaling pathway blocked macrophage-induced invadopodium formation in vitro and the dissemination of tumor cells from the primary tumor in vivo. Our findings indicate a novel role for Notch1 signaling in the regulation of MenaINV expression and transendothelial migration and provide mechanistic information essential to the use of therapeutic inhibitors of metastasis.read more
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Notch Signaling in the Tumor Microenvironment.
Olivier Meurette,Patrick Mehlen +1 more
TL;DR: How Notch signaling takes an important part in regulating the crosstalk between the different compartments of the TME is discussed and the consequences of the Notch-TME involvement from a therapeutic perspective are addressed.
Journal ArticleDOI
Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism
George S. Karagiannis,Jessica Pastoriza,Yarong Wang,Allison S. Harney,David Entenberg,Jeanine Pignatelli,Ved P. Sharma,Emily A. Xue,Esther Cheng,Timothy M. D'Alfonso,Joan G. Jones,Jesus Anampa,Thomas E. Rohan,Joseph A. Sparano,John S. Condeelis,Maja H. Oktay,Maja H. Oktay +16 more
TL;DR: Results indicate that TMEM score increases and MENA isoform expression pattern changes with chemotherapy and can be used in predicting prometastatic changes in response to chemotherapy.
Journal ArticleDOI
Tumor Cell Invadopodia: Invasive Protrusions that Orchestrate Metastasis.
TL;DR: How the invadopodium is an important conductor that orchestrates tumor cell dissemination during metastasis is discussed.
A Mena Invasion Isoform Potentiates EGF-Induced Carcinoma Cell Invasion and Metastasis
Ulrike Philippar,Evanthia T. Roussos,Matthew G. Oser,Hideki Yamaguchi,Hideki Yamaguchi,Hyung-Do Kim,Silvia Giampieri,Yarong Wang,Sumanta Goswami,Sumanta Goswami,Jeffrey B. Wyckoff,Douglas A. Lauffenburger,Erik Sahai,Erik Sahai,John S. Condeelis,Frank B. Gertler +15 more
TL;DR: In this paper, Mena and Mena(INV) were shown to promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis.
Journal ArticleDOI
Perspective on Circulating Tumor Cell Clusters: Why It Takes a Village to Metastasize
Mario Giuliano,Anum Shaikh,Hin Ching Lo,Grazia Arpino,Sabino De Placido,Xiang Zhang,Massimo Cristofanilli,Rachel Schiff,Meghana V. Trivedi +8 more
TL;DR: Insight is provided on existing preclinical evidence on the potential mechanisms leading to CTC cluster formation and dissemination and on processes that may offer survival advantage and on future directions to delineate the role of CTC clusters in metastatic cascade.
References
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