Lipocalin‐2 and matrix metalloproteinase‐9 expression in high‐grade endometrial cancer and their prognostic value

Mihalj, S. Srdelic; Kuzmić-Prusac, Ivana; Zekić-Tomaš, Sandra; Šamija-Projić, Ivana; Čapkun, Vesna

doi:10.1111/his.12633

Cited by 16 publications

(19 citation statements)

References 40 publications

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“…A shorter overall and disease-free survival period was observed in endometrial cancer patients who expressed NGAL [80].…”

Section: Effects Of Ngal On Cancer Progressionmentioning

confidence: 94%

“…Many transcription factors, including the estrogen and androgen receptors, regulate NGAL expression by both positive and negative mechanisms [67][68][69][70][71][72][73][74][75][76][77]. 11 NGAL is an important molecule in many different types of cancer including: breast [9,10,77], colorectal (CRC) [78,79], endometrial [80], esophageal [7,81], gastric cancer [6], liver [82][83][84], lung [85][86][87] ovarian [88], pancreatic [89,90], prostate [76,91], renal [8,92] and thyroid cancer [68]. In general, elevated NGAL expression has been associated with advanced cancer and poor prognosis.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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

Candido

Abrams

Steelman

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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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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“…A shorter overall and disease-free survival period was observed in endometrial cancer patients who expressed NGAL [80].…”

Section: Effects Of Ngal On Cancer Progressionmentioning

confidence: 94%

Section: Accepted Manuscriptmentioning

confidence: 99%

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

Candido

Abrams

Steelman

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Several studies have demonstrated that Lcn2 expression is increased in the presence of acute or chronic inflammation, as well as in cancer (28,29). In addition, Lcn2 is capable of interacting with matrix metalloproteinases via the formation of complexes, and then participating in the cancer cell invasion process (30). Our previous studies showed that NGAL, coded by Lcn2, is associated with the clinical prognosis of glioma (31,32).…”

Section: Introductionmentioning

confidence: 94%

Lcn2-derived Circular RNA (hsa_circ_0088732) Inhibits Cell Apoptosis and Promotes EMT in Glioma via the miR-661/RAB3D Axis

Jin

Liu

et al. 2020

Front. Oncol.

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Background: Glioma is the most common malignant tumor of the central nervous system, and often displays invasive growth. Recently, circular RNA (circRNA), which is a novel non-coding type of RNA, has been shown to play a vital role in glioma tumorigenesis. However, the functions and mechanism of lipocalin-2 (Lcn2)-derived circular RNA (hsa_circ_0088732) in glioma progression remain unclear. Methods: We evaluated hsa_circ_0088732 expression by fluorescence in situ hybridization (FISH), Sanger sequencing, and PCR assays. Cell apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. Transwell migration and invasion assays were performed to measure cell metastasis and viability. In addition, the target miRNA of hsa_circ_0088732 and the target gene of miR-661 were predicted by a bioinformatics analysis, and the interactions were verified by dual-luciferase reporter assays. RAB3D expression was analyzed by an immunochemistry assay, and E-cadherin, N-cadherin, and vimentin protein expression were examined by western blot assays. A mouse xenograft model was developed and used to analyze the effects of hsa_circ_0088732 on glioma growth in vivo. Results: We verified that hsa_circ_0088732 is circular and highly expressed in glioma tissues. Knockdown of hsa_circ_0088732 induced glioma cell apoptosis and inhibited glioma cell migration, invasion, and epithelial-mesenchymal transition (EMT). We found that hsa_circ_0088732 negatively regulated miR-661 by targeting miR-661, and RAB3D was a target gene of miR-661. In addition, inhibition of miR-661 promoted glioma cell metastasis and suppressed cell apoptosis. Knockdown of RAB3D induced cell apoptosis and suppressed cell metastasis. Moreover, hsa_circ_0088732 accelerated glioma progression through its effects on the miR-661/RAB3D axis. Finally, results from a mouse xenograft model confirmed that knockdown of hsa_circ_0088732 induced miR-661 expression, resulting in suppression of RAB3D expression and inhibition of tumor growth in vivo. Jin et al. hsa_circ_0088732 Acts as an Oncogene in Glioma Conclusion: We demonstrated that hsa_circ_0088732 facilitated glioma progression by sponging miR-661 to increase RAB3D expression. This study provides a theoretical basis for understanding the development and occurrence of glioma, as well as for the development of targeted drugs.

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“…LCN2 expression levels are particularly high in breast, pancreas, ovarian, colorectal, thyroid, and bile duct cancer tissues and cell lines derived from these tumors [27,[29][30][31][32][33][34][35]. Table 1 summarizes various studies reporting LCN2 expression levels and LCN2 s function in several cancer types.…”

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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Lipocalin‐2 and matrix metalloproteinase‐9 expression in high‐grade endometrial cancer and their prognostic value

Abstract: Our findings suggest that LCN-2 expression may be an important independent indicator of shorter survival in patients with high-grade endometrial cancer.

Cited by 16 publications

References 40 publications

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

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

Lcn2-derived Circular RNA (hsa_circ_0088732) Inhibits Cell Apoptosis and Promotes EMT in Glioma via the miR-661/RAB3D Axis

Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer

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