Macrophage-derived lipocalin-2 transports iron in the tumor microenvironment

Research output: Contribution to journalArticle

Abstract

While the importance of iron for tumor development is widely appreciated, the exact sources of tumor-supporting iron largely remain elusive. The possibility that iron might be provided by stromal cells in the tumor microenvironment was not taken into account so far. In the present study, we show that tumor-associated macrophages (TAM) acquire an iron-release phenotype upon their interaction with tumor cells, thereby increasing the availability of iron in the tumor microenvironment. Mechanistically, TAM expressed elevated levels of the high-affinity iron-binding protein lipocalin-2 (LCN-2), which appeared to be critical for the export of iron from TAM, and in turn enhanced tumor cell proliferation. Moreover, in PyMT-mouse tumors as well as in primary human breast tumors LCN-2 was predominantly expressed in the tumor stroma as compared to tumor cells. LCN-2 expression in the stroma further correlated with enhanced tumor proliferation in vivo. Our data suggest a dominant role of TAM in the tumor iron-management and identify LCN-2 as a critical iron transporter in this context. Targeting the LCN-2 iron export mechanism selectively in stromal cells might open for future iron-targeted tumor therapeutic approaches.

Details

Authors
Organisations
External organisations
  • Goethe University
  • University of Costa Rica
  • Temple University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • iron, iron-trafficking, lipocalin-2, TAM, tumor microenvironment, tumor stroma
Original languageEnglish
Article numbere1408751
JournalOncoImmunology
Volume7
Issue number3
Early online date2017 Dec 22
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes