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

Chiang, Kun‐Chun; Yeh, Ta‐Sen; Wu, Ren‐Chin; Pang, Jong‐Hwei S.; Cheng, Chi‐Tung; Wang, Shang‐Yu; Juang, Horng‐Heng; Yeh, Chun‐Nan

doi:10.1038/srep36138

Cited by 42 publications

(31 citation statements)

References 44 publications

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“…We have also used western blot analysis to validate the NGAL from conditioned media and to confirm its presence in plasma of cancer patients (unpublished data). Our result corresponds to a recent report on lipocalin-2 as a potential biomarker for CCA (27).…”

Section: Discussionsupporting

confidence: 92%

Secretomic profiling of cells from hollow fiber bioreactor reveals PSMA3 as a potential cholangiocarcinoma biomarker

Verathamjamras

Weeraphan

Chokchaichamnankit

et al. 2017

International Journal of Oncology

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Cholangiocarcinoma (CCA), derived from the bile duct, occurs with a relatively high incidence in Northeast Thailand. Early diagnosis is still hampered by the lack of sufficient biomarkers. In recent years, biomarker discovery using secretomes has provided interesting results, including our studies on CCA secretomes, especially with three-dimensional cell cultures. Thus, cells cultured using the hollow fiber bioreactor (HFB) with 20 kDa molecular weight cut-off (MWCO) yielded higher quality and quantity of secretomes than those from conditioned media of the monolayer culture (MNC) system. In this study, we employed the HFB culture system with 5 kDa MWCO and compared conditioned media from the HFB and MNC systems using two-dimensional gel electrophoresis, followed by identifying proteins of interest by liquid chromatography and mass spectrometry (LC/MS/MS). Two out of 4 spots of NGAL or lipocalin-2 were found to show highest increase in expression of 19.93-fold and 18.79-fold in HFB compared to MNC. Interestingly, all 14 proteasome subunits including proteasome subunit α type-1 to type-7 and β type-1 to type-7 showed 2.92-fold to 12.13-fold increased expression in HFB. The protein-protein interactions of upregulated proteins were predicted, and one of the main interaction clusters involved 20S proteasome subunits. Proteasome activity in the HFB conditioned media was also found to be higher than that in MNC conditioned media. Three types of proteasome subunit were also validated by immunoblotting and showed higher expression in the HFB system compared to MNC system. Proteasome subunit α type-3 (PSMA3) showed the highest level in plasma of cholangiocarcinoma patients compared to normal and hepatocellular carcinoma patients by immunodetection, and is of interest as a potential biomarker for cholangiocarcinoma.

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Section: Discussionsupporting

confidence: 92%

Secretomic profiling of cells from hollow fiber bioreactor reveals PSMA3 as a potential cholangiocarcinoma biomarker

Verathamjamras

Weeraphan

Chokchaichamnankit

et al. 2017

International Journal of Oncology

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“…An interrogation of The Cancer Genome Atlas (TCGA) data portal showed that several cancers have significantly altered expression of LCN2 compared to normal tissue, suggesting LCN2's potential as a prognostic biomarker [39] (Figure 1). Some studies have correlated upregulated LCN2 expression in tumor tissue with poor outcomes caused by increased growth of cancer cells, therapeutic resistance, invasion, and metastasis [27,28,36,40,41]. Similarly, Bauer et al analyzed 207 well-characterized breast cancer tumor tissues by IHC and observed a significant correlation between high LCN2 levels and negative estrogen receptor expression [36].…”

Section: Lcn2 Expression In Cancermentioning

confidence: 99%

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

Santiago-Sánchez

Pita-Grisanti

Quiñones-Díaz

et al. 2020

IJMS

102

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Lipocalin-2 (LCN2) is a secreted glycoprotein linked to several physiological roles, including transporting hydrophobic ligands across cell membranes, modulating immune responses, maintaining iron homeostasis, and promoting epithelial cell differentiation. Although LNC2 is expressed at low levels in most human tissues, it is abundant in aggressive subtypes of cancer, including breast, pancreas, thyroid, ovarian, colon, and bile duct cancers. High levels of LCN2 have been associated with increased cell proliferation, angiogenesis, cell invasion, and metastasis. Moreover, LCN2 modulates the degradation, allosteric events, and enzymatic activity of matrix metalloprotease-9, a metalloprotease that promotes tumor cell invasion and metastasis. Hence, LCN2 has emerged as a potential therapeutic target against many cancer types. This review summarizes the most relevant findings regarding the expression, biological roles, and regulation of LCN2, as well as the proteins LCN2 interacts with in cancer. We also discuss the approaches to targeting LCN2 for cancer treatment that are currently under investigation, including the use of interference RNAs, antibodies, and gene editing.

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“…Recent research has shown that the transferrin-independent iron transport mechanism existed in the tumor microenvironment, and these transport mechanisms were dependent on the key molecules of lipocalin2 (LCN2) and siderophores [ 119 ]. LCN2 is also up-regulated in some cancers, including breast, cervical and pancreatic cancer, and LCN2 expression correlates with increased invasiveness and poor prognosis [ 89 , 90 , 91 , 92 ]. The expression of LCN2 influences the prostate cancer cells growth and invasion via activating ERK signaling pathway [ 90 , 120 ].…”

Section: Alterations Of Iron Homeostasis In Cancer Cellsmentioning

confidence: 99%

Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer

Zhou

Zhao

Zhang

et al. 2018

IJMS

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Iron is an essential element for the growth and proliferation of cells. Cellular iron uptake, storage, utilization and export are tightly regulated to maintain iron homeostasis. However, cellular iron metabolism pathways are disturbed in most cancer cells. To maintain rapid growth and proliferation, cancer cells acquire large amounts of iron by altering expression of iron metabolism- related proteins. In this paper, normal cellular iron metabolism and the alterations of iron metabolic pathways in cancer cells were summarized. Therapeutic strategies based on targeting the altered iron metabolism were also discussed and disrupting redox homeostasis by intracellular high levels of iron provides new insight for cancer therapy. Altered iron metabolism constitutes a promising therapeutic target for cancer therapy.

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

Cited by 42 publications

References 44 publications

Secretomic profiling of cells from hollow fiber bioreactor reveals PSMA3 as a potential cholangiocarcinoma biomarker

Secretomic profiling of cells from hollow fiber bioreactor reveals PSMA3 as a potential cholangiocarcinoma biomarker

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer

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