6533b7dcfe1ef96bd1272ae0

RESEARCH PRODUCT

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

Lucio CoccoJames A. MccubreyGiuseppe MontaltoSaverio CandidoAlberto M. MartelliKvin LertpiriyapongStephen L. AbramsMassimo LibraLinda S. SteelmanMelchiorre CervelloTimothy L. FitzgeraldJerry Polesel

subject

0301 basic medicinemedicine.medical_treatmentDrug resistance; Iron transport; Lcn2; Lipocalins; MMP-9; NGAL; SiderocalinsAcute-Phase ProteinLipocalinLipocalinMetastasisTargeted therapyAntineoplastic Agent0302 clinical medicineNeoplasmsTumor MicroenvironmentNeoplasm MetastasisNGALProto-Oncogene ProteinMedicine (all)SiderocalinsLipocalinsNeoplasm MetastasiMatrix Metalloproteinase 9030220 oncology & carcinogenesismedicine.symptomSignal transductionMMP-9HumanProtein BindingSignal TransductionSiderocalinAntineoplastic AgentsInflammationBiologyModels Biological03 medical and health sciencesLcn2Lipocalin-2Proto-Oncogene ProteinsmedicineHumansIron transportMolecular BiologyTumor microenvironmentInnate immune systemCell Biologymedicine.disease030104 developmental biologyDrug resistanceCancer cellImmunologyCancer researchNeoplasmAcute-Phase Proteins

description

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.

10.1016/j.bbamcr.2015.08.010http://hdl.handle.net/11585/545366