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Targeting tumor-associated macrophages as a novel strategy against breast cancer

Academic Article
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Overview

authors

  • Luo, Y. P.
  • Zhou, H.
  • Krueger, J.
  • Kaplan, C.
  • Lee, S. H.
  • Dolman, C.
  • Markowitz, D.
  • Wu, W. Y.
  • Liu, C.
  • Reisfeld, Ralph
  • Xiang, R.

publication date

  • August 2006

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Tumor-associated macrophages (TAMs) are associated with tumor progression and metastasis. Here, we demonstrate for the first time that legumain, a member of the asparaginyl endopeptidase family functioning as a stress protein, overexpressed by TAMs, provides an ideal target molecule. In fact, a legumain-based DNA vaccine served as a tool to prove this point, as it induced a robust CD8+ T cell response against TAMs, which dramatically reduced their density in tumor tissues and resulted in a marked decrease in proangiogenic factors released by TAMs such as TGF-beta, TNF-alpha, MMP-9, and VEGF. This, in turn, led to a suppression of both tumor angiogenesis and tumor growth and metastasis. Importantly, the success of this strategy was demonstrated in murine models of metastatic breast, colon, and non-small cell lung cancers, where 75% of vaccinated mice survived lethal tumor cell challenges and 62% were completely free of metastases. In conclusion, decreasing the number of TAMs in the tumor stroma effectively altered the tumor microenvironment involved in tumor angiogenesis and progression to markedly suppress tumor growth and metastasis. Gaining better insights into the mechanisms required for an effective intervention in tumor growth and metastasis may ultimately lead to new therapeutic targets and better anticancer strategies.

subject areas

  • Animals
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cytotoxicity, Immunologic
  • Disease Progression
  • Female
  • Immunohistochemistry
  • Lymphocyte Activation
  • Macrophages
  • Mammary Neoplasms, Animal
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • T-Lymphocytes
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci27648

PubMed ID

  • 16862213
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Additional Document Info

start page

  • 2132

end page

  • 2141

volume

  • 116

issue

  • 8

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