NGAL promotes recruitment of tumor infiltrating leukocytes

Abstract

// Francesco Pacifico 1 , Luna Pisa 2 , Stefano Mellone 1 , Michele Cillo 2 , Alessio Lepore 2 and Antonio Leonardi 2 1 Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, 80131 Naples, Italy 2 Dipartimento 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.