Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma

Miyamoto, Tsutomu; Asaka, Ryoichi; Suzuki, Asuka; Takatsu, Akiko; Kashima, Hiroyasu; Shiozawa, Tanri

doi:10.1016/j.yexmp.2011.06.002

Cited by 30 publications

(31 citation statements)

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“…While there is a limited amount of research published for SLC22A17, recent reports have indicated that its expression is correlated with malignancy. For instance, overexpression of both LCN2 and SLC22A17 has been associated with a worse prognosis in gliomas, hepatocellular and endometrial cancer [47–49]. Moreover, we observed that Lcn2 is also upregulated in the serum after HFD consumption in animals that express pancreas-specific mutant KRas .…”

Section: Discussionmentioning

confidence: 71%

“…Both SLC22A17 and LRP2 have been reported to bind and mediate the cellular uptake of LCN2 [43–45]. While SLC22A17 has been shown to bind specifically to LCN2, LRP2 also binds numerous structurally unrelated molecules including aprotinin, vitamin D3, transferrin and lactoferrin [46, 47]. While there is a limited amount of research published for SLC22A17, recent reports have indicated that its expression is correlated with malignancy.…”

Section: Discussionmentioning

confidence: 99%

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Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment

et al. 2017

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Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation and PDAC development. Mice with acinar cell-specific expression of KrasG12D were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content. Pancreas were collected and analyzed for inflammation, pancreatic intraepithelial neoplasia (PanIN) and PDAC. We also used a syngeneic orthotopic PDAC mouse model to study tumor growth in the presence or absence of Lcn2 expression. In addition, to understand the mechanistic role of how LCN2 could be mediating PDAC, we studied LCN2 and its specific receptor solute carrier family 22 member 17 (SLC22A17) in human pancreatic cancer stellate cells (PSC), key mediators of the PDAC stroma. Depletion of Lcn2 diminished extracellular matrix deposition, immune cell infiltration, PanIN formation and tumor growth. Notably, it also increased survival in both obesity-driven and syngeneic orthotopic PDAC mouse models. LCN2 modulated the secretion of pro-inflammatory cytokines in PSC of the PDAC tumor microenvironment, while downregulation of LCN2-specific receptor SLC22A17 blocked these effects. Our results reveal how LCN2 acts in the tumor microenvironment links obesity, inflammation and PDAC development.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment

et al. 2017

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“…The decreased expression of CLU thus promotes the cancerous disease condition. LCN2 encodes a 25 kDa secretory protein involved with iron-transportation and contributes to endometrial carcinoma [66]. Moreover, it is a key molecule in various signalling pathways (Additional file 4).…”

Section: Resultsmentioning

confidence: 99%

Identification of ovarian cancer associated genes using an integrated approach in a Boolean framework

2013

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BackgroundCancer is a complex disease where molecular mechanism remains elusive. A systems approach is needed to integrate diverse biological information for the prognosis and therapy risk assessment using mechanistic approach to understand gene interactions in pathways and networks and functional attributes to unravel the biological behaviour of tumors.ResultsWe weighted the functional attributes based on various functional properties observed between cancerous and non-cancerous genes reported from literature. This weighing schema was then encoded in a Boolean logic framework to rank differentially expressed genes. We have identified 17 genes to be differentially expressed from a total of 11,173 genes, where ten genes are reported to be down-regulated via epigenetic inactivation and seven genes are up-regulated. Here, we report that the overexpressed genes IRAK1, CHEK1 and BUB1 may play an important role in ovarian cancer. We also show that these 17 genes can be used to form an ovarian cancer signature, to distinguish normal from ovarian cancer subjects and that the set of three genes, CHEK1, AR, and LYN, can be used to classify good and poor prognostic tumors.ConclusionWe provided a workflow using a Boolean logic schema for the identification of differentially expressed genes by integrating diverse biological information. This integrated approach resulted in the identification of genes as potential biomarkers in ovarian cancer.

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“…Validation by immunohistochemistry confirmed the increase of LCN2 expression from atypical endometrial hyperplasia to carcinomas [22]. High expression of LCN2 protein together with its receptor SLC22A17 has been related to poorer prognosis among endometrial cancer patients [23]. LCN2 mRNA levels have been associated with different EMT-related genes in a study of endometrial hyperplasia [24].…”

Section: Introductionmentioning

confidence: 98%

Lipocalin 2 expression is associated with aggressive features of endometrial cancer

et al. 2012

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BackgroundIncreased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival.MethodsImmunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies.ResultsExpression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage.ConclusionIncreased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.

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Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma

Abstract: Background: We previously reported the overexpression of lipocalin2 (LCN2), a

Cited by 30 publications

References 32 publications

Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment

Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment

Identification of ovarian cancer associated genes using an integrated approach in a Boolean framework

Lipocalin 2 expression is associated with aggressive features of endometrial cancer

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