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

Candido, Saverio; Abrams, Stephen L.; Steelman, Linda S.; Lertpiriyapong, Kvin; Fitzgerald, Timothy L.; Martelli, Alberto M.; Cocco, Lucio; Montalto, Giuseppe; Cervello, Melchiorre; Polesel, Jerry; Libra, Massimo; McCubrey, James A.

doi:10.1016/j.bbamcr.2015.08.010

Cited by 75 publications

(51 citation statements)

References 157 publications

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“…LCN2 has been shown to be able to render cancer cells more resistant to chemotherapy and target therapy44 and has been adversely associated with cancer patients’ survival4546. In our current study, higher LCN2 expression was linked with poor OS of patients with CCA (Fig.…”

Section: Discussionsupporting

confidence: 56%

Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

Chiang

Yeh

et al. 2016

Sci Rep

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Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 (LCN2) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of LCN2 in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 (NDRG1) and NDRG2, known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher LCN2 expression was associated with worse survival in patients with CCA. LCN2 is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA.

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Section: Discussionsupporting

confidence: 56%

Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

Chiang

Yeh

et al. 2016

Sci Rep

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“…We recently observed that NGAL/MMP-9 complex plays an active role in proliferation, differentiation, tissue development, and tumor development of bladder cancer progression [21]. Of note, NGAL and MMP-9 are molecules that are found in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, we have recently demonstrated the involvement of NGAL and MMP-9 in bladder cancer development and progression [20]. The role of these proteins in tumor invasion and metastatic dissemination is largely known as they interact with each other forming the NGAL/MMP-9 complex that in turn promotes the extracellular matrix degradation process necessary for tumor spreading [21, 22]. Therefore, it was intriguing to identify which miRNAs may be able to modulate the expression of such proteins in bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer

et al. 2016

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Bladder cancer is one of the leading cancer of the urinary tract. It is often diagnosed at advanced stage of the disease. To date, no specific and effective early detection biomarkers are available. Cancer development and progression are associated with the involvement of both epithelial-mesenchymal transition (EMT) and tumor microenvironment of which NGAL/MMP-9 complex represents the main player in bladder cancer. It is known that change in microRNAs (miRNAs) expression may result in gene modulation. Therefore, the identification of specific miRNAs associated with EMT pathway and NGAL/MMP-9 complex may be useful to detect the development of bladder cancer at early stages.On this ground, the expression levels of miRNAs in public available datasets of bladder cancer containing data of non-coding RNA profiling was evaluated. This analysis revealed a group of 16 miRNAs differentially expressed between bladder cancer patients and related healthy controls. By miRNA prediction tool (mirDIP), the relationship between the identified miRNAs and the EMT genes was established. Using the DIANA-mirPath (v.2) software, miRNAs, able to modulate the expression of NGAL and MMP-9 genes, were recognized.The results of this study provide evidence that the downregulated hsa-miR-145-5p and hsa-miR-214-3p may modulate the expression of both EMT and NGAL/MMP-9 pathways. Therefore, further validation analyses may confirm the usefulness of these selected miRNAs for predicting the development of bladder cancer at the early stage of the disease.

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“…In particular, lipocalin-2, also known as neutrophil gelatinase-associated lipocalin (NGAL), has been associated with several forms of cancer and shown to promote cellular proliferation. High levels of NGAL indicate advanced stages of cancer, making this protein a potential marker in the diagnosis of several types of tumours (Yang et al, 2009;Rodvold, Mahadevan & Zanetti, 2012;Candido et al, 2014Candido et al, , 2016.…”

Section: (3) Regeneration and Developmentmentioning

confidence: 99%

Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects

et al. 2017

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Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are regarded as carriers of pheromones and odorants in insect chemoreception. These proteins are typically located in antennae, mouth organs and other chemosensory structures; however, members of both classes of proteins have been detected recently in other parts of the body and various functions have been proposed. The best studied of these non-sensory tasks is performed in pheromone glands, where OBPs and CSPs solubilise hydrophobic semiochemicals and assist their controlled release into the environment. In some cases the same proteins are expressed in antennae and pheromone glands, thus performing a dual role in receiving and broadcasting the same chemical message. Several reports have described OBPs and CSPs in reproductive organs. Some of these proteins are male specific and are transferred to females during mating. They likely carry semiochemicals with different proposed roles, from inhibiting other males from approaching mated females, to marking fertilized eggs, but further experimental evidence is still needed. Before being discovered in insects, the presence of binding proteins in pheromone glands and reproductive organs was widely reported in mammals, where vertebrate OBPs, structurally different from OBPs of insects and belonging to the lipocalin superfamily, are abundant in rodent urine, pig saliva and vaginal discharge of the hamster, as well as in the seminal fluid of rabbits. In at least four cases CSPs have been reported to promote development and regeneration: in embryo maturation in the honeybee, limb regeneration in the cockroach, ecdysis in larvae of fire ants and in promoting phase shift in locusts. Both OBPs and CSPs are also important in nutrition as solubilisers of lipids and other essential components of the diet. Particularly interesting is the affinity for carotenoids of CSPs abundantly secreted in the proboscis of moths and butterflies and the occurrence of the same (or very similar CSPs) in the eyes of the same insects. A role as a carrier of visual pigments for these proteins in insects parallels that of retinol-binding protein in vertebrates, a lipocalin structurally related to OBPs of vertebrates. Other functions of OBPs and CSPs include anti-inflammatory action in haematophagous insects, resistance to insecticides and eggshell formation. Such multiplicity of roles and the high success of both classes of proteins in being adapted to different situations is likely related to their stable scaffolding determining excellent stability to temperature, proteolysis and denaturing agents. The wide versatility of both OBPs and CSPs in nature has suggested several different uses for these proteins in biotechnological applications, from biosensors for odours to scavengers for pollutants and controlled releasers of chemicals in the environment.

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

Cited by 75 publications

References 157 publications

Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer

Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects

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