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Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy.

Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology & Functional Genomics, Section of Pathology & Oncology, Via Androne, University of Catania, Catania, Italy. Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA. Department of Comparative Medicine, Brody School of Medicine, East Carolina University, USA. Department of Surgery, Brody School of Medicine, East Carolina University, USA. Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy. Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy; Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare "Alberto Monroy", Palermo, Italy. Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare "Alberto Monroy", Palermo, Italy. Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy. Department of Biomedical and Biotechnological Sciences, Laboratory of Translational Oncology & Functional Genomics, Section of Pathology & Oncology, Via Androne, University of Catania, Catania, Italy. Electronic address: mlibra@unict.it. Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA. Electronic address: mccubreyj@ecu.edu.

Biochimica et biophysica acta. 2016;(3):438-448
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Abstract

Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival in the tumor microenvironment as well as metastasis. Innate immunity is also regulated by NGAL as it can have bacteriostatic properties. NGAL and MMP-9 expression may also affect the sensitivity of cancer cells to chemotherapy as well as targeted therapy. Thus NGAL and MMP-9 play important roles in key processes involved in metastasis as well as response to therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

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Publication Type : Review

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