IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion Journal Article

   

Authors:	Gocheva, V.; Wang, H. W.; Gadea, B. B.; Shree, T.; Hunter, K. E.; Garfall, A. L.; Berman, T.; Joyce, J. A.
Article Title:	IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion
Abstract:	Innate immune cells can constitute a substantial proportion of the cells within the tumor microenvironment and have been associated with tumor malignancy in patients and animal models of cancer; however, the mechanisms by which they modulate cancer progression are incompletely understood. Here, we show that high levels of cathepsin protease activity are induced in the majority of macrophages in the microenvironment of pancreatic islet cancers, mammary tumors, and lung metastases during malignant progression. We further show that tumor-associated macrophage (TAM)-supplied cathepsins B and S are critical for promoting pancreatic tumor growth, angiogenesis, and invasion in vivo, and markedly enhance the invasiveness of cancer cells in culture. Finally, we demonstrate that interleukin-4 (IL-4) is responsible for inducing cathepsin activity in macrophages in vitro and in vivo. Together, these data establish IL-4 as an important regulator, and cathepsin proteases as critical mediators, of the cancer-promoting functions of TAMs. © 2010 by Cold Spring Harbor Laboratory Press.
Keywords:	controlled study; cancer growth; nonhuman; pancreas cancer; pancreatic neoplasms; neoplasms; tumor associated leukocyte; animal cell; mouse; animals; mice; animal tissue; breast cancer; lung neoplasms; interleukin 4; tumor markers, biological; animal experiment; animal model; in vivo study; enzyme activity; cell line, tumor; angiogenesis; neovascularization, pathologic; animalia; mice, transgenic; cancer invasion; lung metastasis; innate immunity; neoplasm invasiveness; microenvironment; cathepsin; cathepsin b; proteinase; cathepsins; macrophages; malignant transformation; invasion; enzyme induction; mammary neoplasms, experimental; protease; interleukin-4; tumor microenvironment; cysteine cathepsin; cathepsin s; tumor-associated macrophage
Journal Title:	Genes and Development
Volume:	24
Issue:	3
ISSN:	0890-9369
Publisher:	Cold Spring Harbor Laboratory Press
Date Published:	2010-02-01
Start Page:	241
End Page:	255
Language:	English
DOI:	10.1101/gad.1874010
PUBMED:	20080943
PROVIDER:	scopus
PMCID:	PMC2811826
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-76149146398&partnerID=40&md5=eb93c84d4e50e23e6a6b56f9228a8c2a
Notes:	--- - "Cited By (since 1996): 23" - "Export Date: 20 April 2011" - "CODEN: GEDEE" - "Source: Scopus"

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