Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1

Research output: Contribution to journalArticle

Tina El Rayes, Raúl Catena, Sharrell Lee, Marcin Stawowczyk, Natasha Joshi, Claudia Fischbach, Charles A. Powell, Andrew Dannenberg, Nasser K. Altorki, Dingcheng Gao, Vivek Mittal

Inflammation is inextricably associated with primary tumor progression. However, the contribution of inflammation to tumor outgrowth in metastatic organs has remained underexplored. Here, we show that extrinsic inflammation in the lungs leads to the recruitment of bone marrow-derived neutrophils, which degranulate azurophilic granules to release the Ser proteases, elastase and cathepsin G, resulting in the proteolytic destruction of the antitumorigenic factor thrombospondin-1 (Tsp-1). Genetic ablation of these neutrophil proteases protected Tsp-1 from degradation and suppressed lung metastasis. These results provide mechanistic insights into the contribution of inflammatory neutrophils to metastasis and highlight the unique neutrophil protease-Tsp-1 axis as a potential antimetastatic therapeutic target.

Original languageEnglish (US)
Pages (from-to)16000-16005
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number52
DOIs
StatePublished - Dec 29 2015

PMID: 26668367

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Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. / Rayes, Tina El; Catena, Raúl; Lee, Sharrell; Stawowczyk, Marcin; Joshi, Natasha; Fischbach, Claudia; Powell, Charles A.; Dannenberg, Andrew; Altorki, Nasser K.; Gao, Dingcheng; Mittal, Vivek.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 52, 29.12.2015, p. 16000-16005.

Research output: Contribution to journalArticle

Harvard

Rayes, TE, Catena, R, Lee, S, Stawowczyk, M, Joshi, N, Fischbach, C, Powell, CA, Dannenberg, A, Altorki, NK, Gao, D & Mittal, V 2015, 'Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1' Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 52, pp. 16000-16005. https://doi.org/10.1073/pnas.1507294112

APA

Rayes, T. E., Catena, R., Lee, S., Stawowczyk, M., Joshi, N., Fischbach, C., ... Mittal, V. (2015). Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. Proceedings of the National Academy of Sciences of the United States of America, 112(52), 16000-16005. https://doi.org/10.1073/pnas.1507294112

Vancouver

Rayes TE, Catena R, Lee S, Stawowczyk M, Joshi N, Fischbach C et al. Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. Proceedings of the National Academy of Sciences of the United States of America. 2015 Dec 29;112(52):16000-16005. https://doi.org/10.1073/pnas.1507294112

Author

Rayes, Tina El ; Catena, Raúl ; Lee, Sharrell ; Stawowczyk, Marcin ; Joshi, Natasha ; Fischbach, Claudia ; Powell, Charles A. ; Dannenberg, Andrew ; Altorki, Nasser K. ; Gao, Dingcheng ; Mittal, Vivek. / Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 52. pp. 16000-16005.

BibTeX

@article{724272b676734ff380c7a8e3de4a33be,
title = "Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1",
abstract = "Inflammation is inextricably associated with primary tumor progression. However, the contribution of inflammation to tumor outgrowth in metastatic organs has remained underexplored. Here, we show that extrinsic inflammation in the lungs leads to the recruitment of bone marrow-derived neutrophils, which degranulate azurophilic granules to release the Ser proteases, elastase and cathepsin G, resulting in the proteolytic destruction of the antitumorigenic factor thrombospondin-1 (Tsp-1). Genetic ablation of these neutrophil proteases protected Tsp-1 from degradation and suppressed lung metastasis. These results provide mechanistic insights into the contribution of inflammatory neutrophils to metastasis and highlight the unique neutrophil protease-Tsp-1 axis as a potential antimetastatic therapeutic target.",
keywords = "Inflammation, Metastasis, Neutrophils, Proteases, Thrombospondin-1",
author = "Rayes, {Tina El} and Ra{\'u}l Catena and Sharrell Lee and Marcin Stawowczyk and Natasha Joshi and Claudia Fischbach and Powell, {Charles A.} and Andrew Dannenberg and Altorki, {Nasser K.} and Dingcheng Gao and Vivek Mittal",
year = "2015",
month = "12",
day = "29",
doi = "10.1073/pnas.1507294112",
language = "English (US)",
volume = "112",
pages = "16000--16005",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "52",

}

RIS

TY - JOUR

T1 - Lung inflammation promotes metastasis through neutrophil protease-mediated degradation of Tsp-1

AU - Rayes, Tina El

AU - Catena, Raúl

AU - Lee, Sharrell

AU - Stawowczyk, Marcin

AU - Joshi, Natasha

AU - Fischbach, Claudia

AU - Powell, Charles A.

AU - Dannenberg, Andrew

AU - Altorki, Nasser K.

AU - Gao, Dingcheng

AU - Mittal, Vivek

PY - 2015/12/29

Y1 - 2015/12/29

N2 - Inflammation is inextricably associated with primary tumor progression. However, the contribution of inflammation to tumor outgrowth in metastatic organs has remained underexplored. Here, we show that extrinsic inflammation in the lungs leads to the recruitment of bone marrow-derived neutrophils, which degranulate azurophilic granules to release the Ser proteases, elastase and cathepsin G, resulting in the proteolytic destruction of the antitumorigenic factor thrombospondin-1 (Tsp-1). Genetic ablation of these neutrophil proteases protected Tsp-1 from degradation and suppressed lung metastasis. These results provide mechanistic insights into the contribution of inflammatory neutrophils to metastasis and highlight the unique neutrophil protease-Tsp-1 axis as a potential antimetastatic therapeutic target.

AB - Inflammation is inextricably associated with primary tumor progression. However, the contribution of inflammation to tumor outgrowth in metastatic organs has remained underexplored. Here, we show that extrinsic inflammation in the lungs leads to the recruitment of bone marrow-derived neutrophils, which degranulate azurophilic granules to release the Ser proteases, elastase and cathepsin G, resulting in the proteolytic destruction of the antitumorigenic factor thrombospondin-1 (Tsp-1). Genetic ablation of these neutrophil proteases protected Tsp-1 from degradation and suppressed lung metastasis. These results provide mechanistic insights into the contribution of inflammatory neutrophils to metastasis and highlight the unique neutrophil protease-Tsp-1 axis as a potential antimetastatic therapeutic target.

KW - Inflammation

KW - Metastasis

KW - Neutrophils

KW - Proteases

KW - Thrombospondin-1

UR - http://www.scopus.com/inward/record.url?scp=84952683513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952683513&partnerID=8YFLogxK

U2 - 10.1073/pnas.1507294112

DO - 10.1073/pnas.1507294112

M3 - Article

VL - 112

SP - 16000

EP - 16005

JO - Proceedings of the National Academy of Sciences of the United States of America

T2 - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 52

ER -

ID: 18840636