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Angiogenesis
Published in: Angiogenesis 3/2012

01-09-2012 | Original Paper

Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis

Authors: Marek Wagner, Rolf Bjerkvig, Helge Wiig, Juan M. Melero-Martin, Ruei-Zeng Lin, Michael Klagsbrun, Andrew C. Dudley

Published in: Angiogenesis | Issue 3/2012

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Abstract

Tumor-associated stroma is typified by a persistent, non-resolving inflammatory response that enhances tumor angiogenesis, growth and metastasis. Inflammation in tumors is instigated by heterotypic interactions between malignant tumor cells, vascular endothelium, fibroblasts, immune and inflammatory cells. We found that tumor-associated adipocytes also contribute to inflammation. We have analyzed peritumoral adipose tissue in a syngeneic mouse melanoma model. Compared to control adipose tissue, adipose tissue juxtaposed to implanted tumors exhibited reduced adipocyte size, extensive fibrosis, increased angiogenesis and a dense macrophage infiltrate. A mouse cytokine protein array revealed up-regulation of inflammatory mediators including IL-6, CXCL1, MCP-1, MIP-2 and TIMP-1 in peritumoral versus counterpart adipose tissues. CD11b+ macrophages contributed strongly to the inflammatory activity. These macrophages were isolated from peritumoral adipose tissue and found to over-express ARG1, NOS2, CD301, CD163, MCP-1 and VEGF, which are indicative of both M1 and M2 polarization. Tumors implanted at a site distant from subcutaneous, anterior adipose tissue were strongly growth-delayed, had fewer blood vessels and were less populated by CD11b+ macrophages. In contrast to normal adipose tissue, micro-dissected peritumoral adipose tissue explants launched numerous vascular sprouts when cultured in an ex vivo model. Thus, inflamed tumor-associated adipose tissue fuels the growth of malignant cells by acting as a proximate source for vascular endothelium and activated pro-inflammatory cells, in particular macrophages.
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Metadata
Title
Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis
Authors
Marek Wagner
Rolf Bjerkvig
Helge Wiig
Juan M. Melero-Martin
Ruei-Zeng Lin
Michael Klagsbrun
Andrew C. Dudley
Publication date
01-09-2012
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 3/2012
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-012-9276-y

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