Oncotarget

Research Papers:

Canonical NF-κB signaling in myeloid cells promotes lung metastasis in a mouse breast cancer model

Tobias Neumann, Özge Canli and Florian R. Greten _

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Oncotarget. 2018; 9:16775-16791. https://doi.org/10.18632/oncotarget.24697

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Abstract

Tobias Neumann1, Özge Canli1 and Florian R. Greten1,2

1Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt, Germany

2German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany

Correspondence to:

Florian R. Greten, email: greten@gsh.uni-frankfurt.de

Keywords: breast cancer; lung metastasis; inflammation; NF-κB; myeloid cells

Received: November 30, 2017    Accepted: February 25, 2018    Published: March 30, 2018

ABSTRACT

An inflammatory tumor microenvironment is a common characteristic of solid tumors. It is the result of a complex interplay between tumor cells, tumor infiltrating immune cells and other stromal cells. Myeloid cells in the tumor microenvironment are considered major drivers of tumor progression and metastasis and increased numbers of these cells are associated with poor prognosis in various cancer patients. The transcription factor NF-κB is considered the master regulator of inflammatory gene expression and immune cell function. Its activation in various cells of the tumor microenvironment contributes essentially to tumorigenesis. In the present study, the role of canonical NF-κB signaling in myeloid cells in metastatic breast cancer was addressed by myeloid-specific deletion of Ikkβ in the MMTV polyoma middle T (PyMT) mouse model. Ikkβ deletion in myeloid cells did not affect primary mammary tumor growth but significantly reduced lung metastasis. While dissemination from the primary tumor was unaltered, myeloid-specific Ikkβ loss resulted in a strong up-regulation of pro-inflammatory genes and changes in immune cell populations in the lung, creating a tumor-suppressive microenvironment at the distant site. Thus, canonical NF-κB signaling in myeloid cells creates a permissive lung microenvironment that supports breast to lung metastasis.


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PII: 24697