Diverse matrix metalloproteinase functions regulate cancer amoeboid migration

Jose L Orgaz; Pahini Pandya; Rimple Dalmeida; Panagiotis Karagiannis; Berta Sanchez-Laorden; Amaya Viros; Jean Albrengues; Frank O Nestle; Anne J Ridley; Cedric Gaggioli; Richard Marais; Sophia N Karagiannis; Victoria Sanz Moreno

doi:10.1038/ncomms5255

Diverse matrix metalloproteinase functions regulate cancer amoeboid migration

Jose L Orgaz, Pahini Pandya, Rimple Dalmeida, Panagiotis Karagiannis, Berta Sanchez-Laorden, Amaya Viros, Jean Albrengues, Frank O Nestle, Anne J Ridley, Cedric Gaggioli, Richard Marais, Sophia N Karagiannis, Victoria Sanz Moreno

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Abstract

Rounded-amoeboid cancer cells use actomyosin contractility driven by Rho-ROCK and JAK-STAT3 to migrate efficiently. It has been suggested that rounded-amoeboid cancer cells do not require matrix metalloproteinases (MMPs) to invade. Here we compare MMP levels in rounded-amoeboid and elongated-mesenchymal melanoma cells. Surprisingly, we find that rounded-amoeboid melanoma cells secrete higher levels of several MMPs, including collagenase MMP-13 and gelatinase MMP-9. As a result, rounded-amoeboid melanoma cells degrade collagen I more efficiently than elongated-mesenchymal cells. Furthermore, using a non-catalytic mechanism, MMP-9 promotes rounded-amoeboid 3D migration through regulation of actomyosin contractility via CD44 receptor. MMP-9 is upregulated in a panel of rounded-amoeboid compared with elongated-mesenchymal melanoma cell lines and its levels are controlled by ROCK-JAK-STAT3 signalling. MMP-9 expression increases during melanoma progression and it is particularly prominent in the invasive fronts of lesions, correlating with cell roundness. Therefore, rounded-amoeboid cells use both catalytic and non-catalytic activities of MMPs for invasion.

Original language	English
Article number	4255
Number of pages	13
Journal	Nature Communications
Volume	5
Early online date	25 Jun 2014
DOIs	https://doi.org/10.1038/ncomms5255
Publication status	Published - 25 Jun 2014

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title = "Diverse matrix metalloproteinase functions regulate cancer amoeboid migration",

abstract = "Rounded-amoeboid cancer cells use actomyosin contractility driven by Rho-ROCK and JAK-STAT3 to migrate efficiently. It has been suggested that rounded-amoeboid cancer cells do not require matrix metalloproteinases (MMPs) to invade. Here we compare MMP levels in rounded-amoeboid and elongated-mesenchymal melanoma cells. Surprisingly, we find that rounded-amoeboid melanoma cells secrete higher levels of several MMPs, including collagenase MMP-13 and gelatinase MMP-9. As a result, rounded-amoeboid melanoma cells degrade collagen I more efficiently than elongated-mesenchymal cells. Furthermore, using a non-catalytic mechanism, MMP-9 promotes rounded-amoeboid 3D migration through regulation of actomyosin contractility via CD44 receptor. MMP-9 is upregulated in a panel of rounded-amoeboid compared with elongated-mesenchymal melanoma cell lines and its levels are controlled by ROCK-JAK-STAT3 signalling. MMP-9 expression increases during melanoma progression and it is particularly prominent in the invasive fronts of lesions, correlating with cell roundness. Therefore, rounded-amoeboid cells use both catalytic and non-catalytic activities of MMPs for invasion.",

author = "Orgaz, {Jose L} and Pahini Pandya and Rimple Dalmeida and Panagiotis Karagiannis and Berta Sanchez-Laorden and Amaya Viros and Jean Albrengues and Nestle, {Frank O} and Ridley, {Anne J} and Cedric Gaggioli and Richard Marais and Karagiannis, {Sophia N} and {Sanz Moreno}, Victoria",

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AU - Orgaz, Jose L

AU - Pandya, Pahini

AU - Dalmeida, Rimple

AU - Karagiannis, Panagiotis

AU - Sanchez-Laorden, Berta

AU - Viros, Amaya

AU - Albrengues, Jean

AU - Nestle, Frank O

AU - Ridley, Anne J

AU - Gaggioli, Cedric

AU - Marais, Richard

AU - Karagiannis, Sophia N

AU - Sanz Moreno, Victoria

PY - 2014/6/25

Y1 - 2014/6/25

N2 - Rounded-amoeboid cancer cells use actomyosin contractility driven by Rho-ROCK and JAK-STAT3 to migrate efficiently. It has been suggested that rounded-amoeboid cancer cells do not require matrix metalloproteinases (MMPs) to invade. Here we compare MMP levels in rounded-amoeboid and elongated-mesenchymal melanoma cells. Surprisingly, we find that rounded-amoeboid melanoma cells secrete higher levels of several MMPs, including collagenase MMP-13 and gelatinase MMP-9. As a result, rounded-amoeboid melanoma cells degrade collagen I more efficiently than elongated-mesenchymal cells. Furthermore, using a non-catalytic mechanism, MMP-9 promotes rounded-amoeboid 3D migration through regulation of actomyosin contractility via CD44 receptor. MMP-9 is upregulated in a panel of rounded-amoeboid compared with elongated-mesenchymal melanoma cell lines and its levels are controlled by ROCK-JAK-STAT3 signalling. MMP-9 expression increases during melanoma progression and it is particularly prominent in the invasive fronts of lesions, correlating with cell roundness. Therefore, rounded-amoeboid cells use both catalytic and non-catalytic activities of MMPs for invasion.

AB - Rounded-amoeboid cancer cells use actomyosin contractility driven by Rho-ROCK and JAK-STAT3 to migrate efficiently. It has been suggested that rounded-amoeboid cancer cells do not require matrix metalloproteinases (MMPs) to invade. Here we compare MMP levels in rounded-amoeboid and elongated-mesenchymal melanoma cells. Surprisingly, we find that rounded-amoeboid melanoma cells secrete higher levels of several MMPs, including collagenase MMP-13 and gelatinase MMP-9. As a result, rounded-amoeboid melanoma cells degrade collagen I more efficiently than elongated-mesenchymal cells. Furthermore, using a non-catalytic mechanism, MMP-9 promotes rounded-amoeboid 3D migration through regulation of actomyosin contractility via CD44 receptor. MMP-9 is upregulated in a panel of rounded-amoeboid compared with elongated-mesenchymal melanoma cell lines and its levels are controlled by ROCK-JAK-STAT3 signalling. MMP-9 expression increases during melanoma progression and it is particularly prominent in the invasive fronts of lesions, correlating with cell roundness. Therefore, rounded-amoeboid cells use both catalytic and non-catalytic activities of MMPs for invasion.

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DO - 10.1038/ncomms5255

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SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4255

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Diverse matrix metalloproteinase functions regulate cancer amoeboid migration

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