Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer

Tao, Wei; Zhang, Xiaoyu; Zhang, Qi; Yang, Jiaqi; Chen, Qi; Wang, Jianxin; Li, Xiang; Chen, Junye; Ma, Tao; Li, Guogang; Gao, Shunliang; Lou, Jianying; Que, Risheng; Wang, Yi; Dang, Xiaowei; Li, Zheng; Bai, Xueli

doi:10.1016/j.canlet.2019.03.009

Cited by 96 publications

(89 citation statements)

References 39 publications

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“…For example, apart from the earlier mentioned roles of vimentin in IFs and FAs, and as transcriptional regulator of EMT processes, vimentin is also secreted as an extracellular protein and shown to have various functions, including regulation of axonal growth [130] or spheroid formation of glioblastoma cancer stem cells [122]. In addition, growing evidence suggests its role as a cancer biomarker [131,132].…”

Section: Discussionmentioning

confidence: 99%

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

Strouhalova

Přechová

Gandalovičová

et al. 2020

Cancers

187

143

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Intermediate filaments constitute the third component of the cellular skeleton. Unlike actin and microtubule cytoskeletons, the intermediate filaments are composed of a wide variety of structurally related proteins showing distinct expression patterns in tissues and cell types. Changes in the expression patterns of intermediate filaments are often associated with cancer progression; in particular with phenotypes leading to increased cellular migration and invasion. In this review we will describe the role of vimentin intermediate filaments in cancer cell migration, cell adhesion structures, and metastasis formation. The potential for targeting vimentin in cancer treatment and the development of drugs targeting vimentin will be reviewed.

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Section: Discussionmentioning

confidence: 99%

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

Strouhalova

Přechová

Gandalovičová

et al. 2020

Cancers

187

143

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“…Among mutp53-driven hyper-secreted proteins, we identified cofilin (COF1), which is involved in tumor cell migration and invasion by promoting actin cytoskeleton reorganization and cell-cell adhesion regulation and the level of cofilin-1 in patient’s sera is associated with PDAC progression and poor prognosis [ 41 , 42 , 43 ]; calsyntenin-1 (CLSTN1), which plays a fundamental role in cellular adhesion and cell communication and its expression level was increased in sera of patients with lung adenocarcinoma or in ovarian adenocarcinoma cell lines, but the molecular mechanisms of CLSTN1 in cancer still need to be investigated [ 44 , 45 , 46 ]; vimentin (VIME), which is a well-known marker for epithelial-mesenchymal transition (EMT), and elevated levels of circulating vimentin were detected in hepatocellular carcinoma and in circulating tumor cells (CTCs) in PDAC. Notably, the presence of vimentin + CTCs was negatively associated with progression-free survival [ 47 , 48 , 49 ]. We also found that both R273H and R175H p53 mutant isoforms favor the hyper-secretion of the tissue inhibitor matrix metalloproteinase 1 (TIMP1) in PDAC cells.…”

Section: Discussionmentioning

confidence: 99%

The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells

et al. 2020

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The cancer secretome is a rich repository of useful information for both cancer biology and clinical oncology. A better understanding of cancer secretome is particularly relevant for pancreatic ductal adenocarcinoma (PDAC), whose extremely high mortality rate is mainly due to early metastasis, resistance to conventional treatments, lack of recognizable symptoms, and assays for early detection. TP53 gene is a master transcriptional regulator controlling several key cellular pathways and it is mutated in ~75% of PDACs. We report the functional effect of the hot-spot p53 mutant isoforms R175H and R273H on cancer cell secretome, showing their influence on proliferation, chemoresistance, apoptosis, and autophagy, as well as cell migration and epithelial-mesenchymal transition. We compared the secretome of p53-null AsPC-1 PDAC cells after ectopic over-expression of R175H-mutp53 or R273H-mutp53 to identify the differentially secreted proteins by mutant p53. By using high-resolution SWATH-MS technology, we found a great number of differentially secreted proteins by the two p53 mutants, 15 of which are common to both mutants. Most of these secreted proteins are reported to promote cancer progression and epithelial-mesenchymal transition and might constitute a biomarker secreted signature that is driven by the hot-spot p53 mutants in PDAC.

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“…Circulating tumor cell studies in malignant head and neck cancer and pancreatic cancer using CytoSorter ® also shows that CTCs can be used to differentiate diseased patients from healthy people and patients with benign tumors. 18,19 More than 50 techniques have been developed to enrich CTCs in the peripheral blood, based on different physical parameters (size or density) and/or biological characteristics (cell surface markers) between CTCs and blood cells. 23 Detection rates of CTCs in BC patients range from 8% to 55% depending on the detection method used.…”

Section: F I G U R E 2 Circulating Tumor Cellsmentioning

confidence: 99%

“…Therefore, we decided to use CytoSorter ® CTCs detection system in this study and to evaluate its diagnostic potency in BC. The clinical application of CytoSorter ® has been reported in pancreatic cancer and head and neck cancers . CytoSorter ® technology employs the positive selection utilizing a streptavidin nanoarray on CytoChipNano, which can be coated with any desired biotin‐labeled capture antibody (Ab), and immunofluorescence staining, to capture and identify CTCs.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter^® CTC capture system in patients with breast cancer

et al. 2020

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Purpose In this study, we aimed to investigate the viability of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and to evaluate the diagnostic value of CTCs in breast cancer (BC). Methods A total of 366 females patients suspected of having BC and 30 healthy female volunteers were enrolled in this study. CTCs were enriched by CytoSorter®, a microfluidic‐based CTCs capturing platform. CTC detection was performed before operation or biopsy. Based on the biopsy results, patients were divided into two groups, namely patients with BC and patients with benign breast diseases (BBD). Patients with BBD and healthy volunteers were serving as controls. The correlation between CTC enumeration and patients' clinicopathological characteristics was evaluated. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potency of CytoSorter® system in BC. Results Based on the biopsy results, 130 BC patients at different cancer stages and 236 patients with BBD were enrolled in the study. Seven subjects were dropped out from the study. CTCs were detected in 109 of 128 BC patients, in one of 29 healthy volunteers, and in 37 of 232 patients with BBD. Maximum CTC counts detected in BC patients, healthy volunteers, and patients with BBD were 8, 1, and 4, respectively. Statistical analysis showed CTCs could be used to distinguish BC patients from healthy volunteers and patients with BBD (P < .0001). Circulating tumor cells were statistically associated with patients' cancer stage (P = .0126), tumor size (tumor node metastasis [TNM] T stage, P = .0253), cancer type (invasive vs noninvasive, P = .0141), and lymph node metastasis (P = .0436). More CTCs were found in patients at advanced cancer stage or TNM T stage and in patients with invasive tumor or lymph node metastasis. Furthermore, CTC detection rates in BC patients at Tis and T1‐4 stages were 50%, 81.67%, 91.07%, 100%, and 100%, respectively. When the CTC cut‐off value was set to 2, the ROC curve gave an area under the curve (AUC) of 0.86 with a specificity and sensitivity of 95.4% and 76.56%, respectively. Taken together, CTCs could be used as a diagnostic aid in assistance of cancer screening and staging. Conclusion Circulating tumor cells were successfully isolated in BC patients using CytoSorter® system. CTCs can be used to differentiate BC patients from the patients with BBD or healthy volunteers, and as a diagnostic aid for early cancer diagnosis and cancer staging.

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Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer

Cited by 96 publications

References 39 publications

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter^® CTC capture system in patients with breast cancer

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Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer

Cited by 96 publications

References 39 publications

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter® CTC capture system in patients with breast cancer

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Evaluation of the diagnostic value of circulating tumor cells with CytoSorter^® CTC capture system in patients with breast cancer