Nidogen-1: a candidate biomarker for ovarian serous cancer

Li, Lin; Zhang, Ying; Li, Ning; Feng, Lin; Yao, Hongwen; Zhang, Rong; Li, Bin; Li, Xiaoguang; Han, Ning; Gao, Yanning; Xiao, Ting; Wu, Lingying

doi:10.1093/jjco/hyu187

Cited by 25 publications

(29 citation statements)

References 23 publications

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“…Tumor-derived NID1 may thus serve as a new biomarker for lung metastasis. In support of this, previous reports have shown elevated NID1 blood levels in multiple myeloma and ovarian cancer patients compared with healthy controls Khan et al 2014;Li et al 2015). Furthermore, high NID1 levels correlated with advanced stage and reflected tumor burden in ovarian cancer patients (Li et al 2015).…”

Section: Discussionsupporting

confidence: 77%

“…In support of this, previous reports have shown elevated NID1 blood levels in multiple myeloma and ovarian cancer patients compared with healthy controls Khan et al 2014;Li et al 2015). Furthermore, high NID1 levels correlated with advanced stage and reflected tumor burden in ovarian cancer patients (Li et al 2015). In future studies of NID1, serum or plasma levels will need to be assessed in breast cancer and melanoma patients, and association with lung relapse and clinical outcome will need to be correlated to examine its relevance as a blood biomarker.…”

Section: Discussionmentioning

confidence: 64%

“…This is in agreement with its known role in facilitating ECM formation (Aumailley et al 1993;Dziadek 1995;Tunggal et al 2003) and cell attachment to a NID1-containing ECM (Dedhar et al 1992;Dong et al 1995;Yi et al 1998). Furthermore, NID1 was shown to enhance cell motility (Pedrola et al 2015) and is elevated in the blood of cancer patients compared with healthy controls Khan et al 2014;Li et al 2015), making it an attractive candidate for experimental assessment in our lung metastasis models.…”

Section: Nid1 As a Candidate Lung Metastasis Promoter In Breast Cancementioning

confidence: 99%

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Identification of Nidogen 1 as a lung metastasis protein through secretome analysis

et al. 2017

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Secreted proteins play crucial roles in mediating tumor-stroma interactions during metastasis of cancer to different target organs. To comprehensively profile secreted proteins involved in lung metastasis, we applied quantitative mass spectrometry-based proteomics and identified 392 breast cancer-derived and 302 melanoma-derived proteins secreted from highly lung metastatic cells. The cancer-specific lung metastasis secretome signatures (LMSSs) displayed significant prognostic value in multiple cancer clinical data sets. Moreover, we observed a significant overlap of enriched pathways between the LMSSs of breast cancer and melanoma despite an overall small overlap of specific proteins, suggesting that common biological processes are executed by different proteins to enable the two cancer types to metastasize to the lung. Among the novel candidate lung metastasis proteins, Nidogen 1 (NID1) was confirmed to promote lung metastasis of breast cancer and melanoma, and its expression is correlated with poor clinical outcomes. In vitro functional analysis further revealed multiple prometastatic functions of NID1, including enhancing cancer cell migration and invasion, promoting adhesion to the endothelium and disrupting its integrity, and improving vascular tube formation capacity. As a secreted prometastatic protein, NID1 may be developed as a new biomarker for disease progression and therapeutic target in breast cancer and melanoma.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 64%

Section: Nid1 As a Candidate Lung Metastasis Promoter In Breast Cancementioning

confidence: 99%

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Identification of Nidogen 1 as a lung metastasis protein through secretome analysis

et al. 2017

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“…Li and coworkers reported the presence of elevated NID1 levels in the serum of ovarian cancer patients, primarily those with an advanced stage of the disease. 63 Along this line, a high content of a specific fragment of NID1, derived from its degradation by cathepsin-S (CatS) was detected in the serum of NSCLC patients. 64 CatS-degraded NID1 was suggested to reflect the loss of BM integrity, an event typically associated to tumor invasion.…”

Section: Discussionmentioning

confidence: 94%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.

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“…CatS is produced in both tumor cells and tumor-associated macrophages (TAMs) [24], and CatS has been shown to promote growth, angiogenesis, migration, invasion, and mestatasis in different cancer types [24], [25], [26], [27]. As nidogen-1 is a key protein of the BM and CatS is an important protein for cancer biology, this interaction may provide a biological set-point, with increased accuracy for cancer and biomarker development.…”

Section: Introductionmentioning

confidence: 99%

Nidogen-1 Degraded by Cathepsin S can be Quantified in Serum and is Associated with Non–Small Cell Lung Cancer

et al. 2017

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Loss of basement membrane (BM) integrity is typically associated with cancer. Nidogen-1 is an essential component of the BM. Nidogen-1 is a substrate for cathepsin-S (CatS) which is released into the tumor microenvironment. Measuring nidogen-1 degraded by CatS may therefore have biomarker potential in cancer. The aim of this study was to investigate if CatS-degraded nidogen-1 was detectable in serum and a possible biomarker for cancer, a pathology associated with disruption of the BM. A competitive enzyme-linked immunosorbent assay (NIC) was developed with a monoclonal mouse antibody specific for a CatS cleavage site on human nidogen-1. Dilution and spiking recovery, inter- and intravariation, as well as accuracy were evaluated. Serum levels were evaluated in patients with breast cancer, small cell lung cancer (SCLC), and non-SCLC (NSCLC) and in healthy controls. The results indicated that the NIC assay was specific for nidogen-1 cleaved by CatS. Inter- and intraassay variations were 9% and 14%, respectively. NIC was elevated in NSCLC as compared to healthy controls (P < .001), breast cancer (P < .01), and SCLC (P < .5). The diagnostic power (area under the receiver operating characteristics) of NIC for NSCLC as compared to all other samples combined was 0.83 (95% confidence interval: 0.71-0.95), P < .0001. In conclusion, nidogen-1 degraded by CatS can be quantified in serum by the NIC assay. The current data strongly suggest that cathepsin-S degradation of nidogen-1 is strongly associated with NSCLC, which needs validation in larger clinical cohorts.

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Nidogen-1: a candidate biomarker for ovarian serous cancer

Abstract: Our study suggests that plasma nidogen-1 may be used as a diagnostic biomarker for ovarian serous carcinoma and can reflect the tumor burden.

Cited by 25 publications

References 23 publications

Identification of Nidogen 1 as a lung metastasis protein through secretome analysis

Identification of Nidogen 1 as a lung metastasis protein through secretome analysis

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

Nidogen-1 Degraded by Cathepsin S can be Quantified in Serum and is Associated with Non–Small Cell Lung Cancer

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