Oncotarget

Research Papers:

NGAL promotes recruitment of tumor infiltrating leukocytes

Francesco Pacifico, Luna Pisa, Stefano Mellone, Michele Cillo, Alessio Lepore and Antonio Leonardi _

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Oncotarget. 2018; 9:30761-30772. https://doi.org/10.18632/oncotarget.25625

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Abstract

Francesco Pacifico1, Luna Pisa2, Stefano Mellone1, Michele Cillo2, Alessio Lepore2 and Antonio Leonardi2

1Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, 80131 Naples, Italy

2Dipartimento di Medicina Molecolare e Biotecnologie Mediche, “Federico II” University of Naples, 80131 Naples, Italy

Correspondence to:

Antonio Leonardi, email: leonardi@unina.it

Keywords: NF-κB; NGAL; cancer; chemokines; chemotaxis

Received: February 01, 2018     Accepted: May 24, 2018     Published: July 20, 2018

ABSTRACT

We have previously shown that Neutrophil Gelatinase-Associated Lipocalin (NGAL) is strongly expressed in thyroid carcinomas, especially of anaplastic type, where it protects neoplastic cells from serum deprivation-induced apoptosis and enhances tumor invasivity by regulating MMP-9 activity. Here we demonstrate that NGAL-containing conditioned medium from human anaplastic thyroid carcinoma (ATC) cells is able to induce monocyte migration via up-regulation of a number of different chemokines. The enhanced chemokines transcription is due to the NGAL-mediated intracellular iron uptake. Very importantly, mice tumor allografts raised from subcutaneous injection of syngeneic colon carcinoma cell lines, expressing high levels of NGAL, show a dense leukocyte infiltrate which strongly decreases in tumor allografts from NGAL-depleted cell injected mice.

Our results indicate that the NGAL promotes leukocytes recruitment in tumor microenvironment through iron-mediated chemokines production.


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