CTC clusters induced by heparanase enhance breast cancer metastasis

Wei, Rongrui; Sun, Danni; Yang, Hong; Yan, Juan; Zhang, Xiong; Zheng, Xingling; Fu, Xuhong; Geng, Meiyu; Huang, Xun; Ding, Jian

doi:10.1038/aps.2017.189

Cited by 60 publications

(54 citation statements)

References 37 publications

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“…Circulating tumour cells (CTCs) analysis has recently emerged as a liquid biopsy approach for the early diagnosis [1,2], biomarker [3], evaluation of curative efficacy [4], evaluation of relapse [5] and prognostic prediction [6,7] in several solid tumours, including breast cancer [8,9],gastric cancer [10], prostate cancer [11], head and neck cancer [12], bladder cancer [13], and lung cancer [14][15][16]. CTCs also showed the potential efficacy in metastasis cancer, such as metastatic breast cancer [17,18] and colorectal cancer [19].…”

Section: Introductionmentioning

confidence: 99%

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

et al. 2020

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Objective: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer. Method: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18. Results: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm. Conclusions: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.

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Section: Introductionmentioning

confidence: 99%

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

et al. 2020

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show abstract

“…Circulating tumour cells (CTCs) analysis has recently emerged as a liquid biopsy approach for the early diagnosis [1,2] , biomarker [3] , evaluation of curative efficacy [4] , evaluation of relapse [5] and prognostic prediction [6,7] in several solid tumours, including breast cancer [8,9] ,gastric cancer [10] , prostate cancer [11] , head and neck cancer [12] , bladder cancer [13] , and lung cancer [14][15][16] . CTCs also showed the potential efficacy in metastasis cancer, such as metastatic breast cancer [17,18] and colorectal cancer [19] .…”

Section: Introductionmentioning

confidence: 99%

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

Zheng

Zhao

et al. 2019

Preprint

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Objective: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer.Method: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18.Results: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, sub solid nodules and nodules ≥8 mm.Conclusion: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, sub solid nodules and nodules ≥8 mm.

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“…This was concluded because increased Src phosphorylation was observed in cells over expressing heparanase that was mutated in glutamic acids 225 and 343 that comprise the enzyme active site (42), or heparanase that was deleted for the heparin binding domain [amino acids 270-280; 10; (31)] (27,36), indicating that Src activation does not require heparanase enzymatic activity or its interaction with HS. Thus, inhibitors of heparanase activity such as HSmimetics or JG6, a marine-derived oligosaccharide (43,44), are not expected to attenuate this function of heparanase. It is possible, nonetheless, that Src activation is downstream to the activation of the epidermal growth factor receptor (EGFR) (27), focal adhesion kinase (FAK) (44), or integrin (29) by heparanase.…”

Section: Discussionmentioning

confidence: 99%

Heparanase Loosens E-Cadherin-Mediated Cell-Cell Contact via Activation of Src

2020

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Activity of heparanase, responsible for cleavage of heparan sulfate (HS), is strongly implicated in tumor metastasis. This is due primarily to remodeling of the extracellular matrix (ECM) that becomes more prone to invasion by metastatic tumor cells. In addition, heparanase promotes the development of blood and lymph vessels that mobilize disseminated cells to distant organs. Here, we provide evidence for an additional mechanism by which heparanase affects cell motility, namely the destruction of E-cadherin based adherent junctions (AJ). We found that overexpression of heparanase or its exogenous addition results in reduced E-cadherin levels in the cell membrane. This was associated with a substantial increase in the phosphorylation levels of E-cadherin, β-catenin, and p120-catenin, the latter recognized as a substrate of Src. Indeed, we found that Src phosphorylation is increased in heparanase overexpressing cells, associating with a marked decrease in the interaction of E-cadherin with β-catenin, which is instrumental for AJ integrity and cell-cell adhesion. Notably, the association of E-cadherin with β-catenin in heparanase overexpressing cells was restored by Src inhibitor, along with reduced cell migration. These results imply that heparanase promotes tumor metastasis by virtue of its enzymatic activity responsible for remodeling of the ECM, and by signaling aspects that result in Src-mediated phosphorylation of E-cadherin/catenins and loosening of cell-cell contacts that are required for maintaining the integrity of epithelial sheets.

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CTC clusters induced by heparanase enhance breast cancer metastasis

Cited by 60 publications

References 37 publications

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

The combination of CTCs and CEA can help guide the management of patients with SPNs suspected of being lung cancer

Heparanase Loosens E-Cadherin-Mediated Cell-Cell Contact via Activation of Src

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