Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment

Liliana Guzman-Rojas, Roberto Rangel, Ahmad Salameh, Julianna K. Edwards, Eleonora Dondossola, Yun Gon Kim, Alan Saghatelian, Ricardo J. Giordano, Mikhail G. Kolonin, Fernanda I. Staquicini, Erkki Koivunen, Richard L. Sidman, Wadih Arap, Renata Pasqualini

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APNnull mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/ or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.

Original languageEnglish (US)
Pages (from-to)1637-1642
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number5
DOIs
StatePublished - Jan 31 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Lung cancer
  • Melanoma
  • Proteolytic activity
  • ShRNA
  • Tumorigenesis

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