Clinical significance of circulating tumor cells identified by cell-surface vimentin in pancreatic cancer.

e14562 Background: Identification of circulating tumor cells (CTCs) largely rely on epithelial tumor cell marker. Here we sought to interrogate whether cell-surface vimentin could be a biomarker for isolating CTCs potentially with mesenchymal phenotype in pancreatic ductal adenocarcinoma (PDAC). Methods: In total, 100 PDAC patients, 16 patients with intraductal papillary mucinous neoplasm (IPMN), and 30 healthy individuals were enrolled between December 2016 and November 2017. Potential CTCs were captured in 4 ml blood samples by vimentin antibody-coated microfluidic chip. CTCs were defined as vimentin+CD45-Hoechst+. Results: In vitro experiment showed that vimentin was highly expressed on the surface of pancreatic tumor cells with mesenchymal phenotype. Overall, vimentin+ CTCs were detected in 76% of patients with PDAC, but only in 2 out 30 healthy donors. Besides, five patients (31.3%) with IPMN had vimentin+ CTCs, and 10 CTCs were identified in one case. Using a cut-off value of two cells/4 ml of blood, 65% PDAC patients were positive for vimentin+ CTCs , while the positivity rates for the patients with IPMN and the healthy controls were 25% and 0%, respectively. Combined vimentin+ CTCs and CA19-9 offered a favorable diagnostic potency with area under curve of 0.968. Vimentin+ CTCs counts correlated with change of tumor burden for patients undergoing resection ( P < 0.01). Significant reduction of CTCs counts was observed after chemotherapy for subjects responding to treatment ( P < 0.05). The paired analysis showed that CTC counts was higher in portal vein blood than peripheral blood for 10 patients with available samples ( P < 0.05). Patients with 2 or more CTCs detected had more advanced disease and poorer differentiated tumor. In addition, preoperative higher CTCs counts correlated with shortened recurrence-free survival (Log-rank test: P = 0.02). Conclusions: Vimentin+ CTCs serves as a reliable biomarker in pancreatic cancer. The enrichment of potential mesenchymal CTCs could complement the strategy capturing epithelial CTCs, and provides a way to more thoroughly interrogate the biology and clinical significance of CTCs in PDAC.

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Circulating Tumor Cells in Pancreatic Cancer: Current Perspectives

Cancers ◽

10.3390/cancers11111659 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1659 ◽

Cited By ~ 6

Author(s):

Verena Martini ◽

Sylvia Timme-Bronsert ◽

Stefan Fichtner-Feigl ◽

Jens Hoeppner ◽

Birte Kulemann

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Prognostic Markers ◽

Cancer Prognosis ◽

Detection Methods ◽

Ductal Adenocarcinoma ◽

Detection Tool ◽

The Usa ◽

New Biomarkers

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis.” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.

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Clinical Significance of Circulating Tumor Cells in Pancreatic Cancer

Biology and Medicine ◽

10.4172/0974-8369.1000357 ◽

2016 ◽

Vol 08 (07) ◽

Author(s):

Guangfu Li ◽

Yue Huang ◽

Yariswamy Manjunath ◽

Eric T Kimchi

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Clinical Significance

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Novel 3D µtissues Mimicking the Fibrotic Stroma in Pancreatic Cancer to Study Cellular Interactions and Stroma-Modulating Therapeutics

Cancers ◽

10.3390/cancers13195006 ◽

2021 ◽

Vol 13 (19) ◽

pp. 5006

Author(s):

Kunal P. Pednekar ◽

Marcel A. Heinrich ◽

Joop van Baarlen ◽

Jai Prakash

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Treatment Options ◽

Treatment Strategies ◽

Collagen Gel ◽

Current Treatment ◽

Ductal Adenocarcinoma ◽

Tumor Type ◽

Cellular Interactions

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor type with low patient survival due to the low efficacy of current treatment options. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) create a dense fibrotic environment around the tumor cells, preventing therapies from reaching their target. Novel 3D in vitro models are needed that mimic this fibrotic barrier for the development of therapies in a biologically relevant environment. Here, novel PDAC microtissues (µtissues) consisting of pancreatic cancer cell core surrounded by a CAF-laden collagen gel are presented, that is based on the cells own contractility to form a hard-to-penetrate barrier. The contraction of CAFs is demonstrated facilitating the embedding of tumor cells in the center of the µtissue as observed in patients. The µtissues displayed a PDAC-relevant gene expression by comparing their gene profile with transcriptomic patient data. Furthermore, the CAF-dependent proliferation of cancer cells is presented, as well as the suitability of the µtissues to serve as a platform for the screening of CAF-modulating therapies in combination with other (nano)therapies. It is envisioned that these PDAC µtissues can serve as a high-throughput platform for studying cellular interactions in PDAC and for evaluating different treatment strategies in the future.

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The clinical significance of circulating tumor cells and T lymphocyte subtypes in pancreatic cancer patients

Bioengineered ◽

10.1080/21655979.2021.2023800 ◽

2022 ◽

Vol 13 (2) ◽

pp. 2130-2138

Author(s):

Yasi Xing ◽

Xinfa Zhang ◽

Fangyuan Qin ◽

Jingwen Yang ◽

Lei Ai ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Clinical Significance ◽

T Lymphocyte

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C5aR correlated with the dissemination capacity of circulating tumor cells in hepatocellular carcinoma by targeting INHBA-p-smad2/3-EMT/MMPs axis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16649 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16649-e16649

Author(s):

Qian Dai ◽

Jie Zhu ◽

Minna Shen ◽

Huiqin Jiang ◽

Baishen Pan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Mouse Model ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Mesenchymal Phenotype ◽

Cell Functions ◽

Tumor Dissemination ◽

C5ar Expression ◽

The Difference

e16649 Background: Circulating tumor cells (CTCs) play important role in tumor dissemination and is an independent survival predictor in Hepatocellular carcinoma (HCC) patients. The aim of this study was to investigate C5a/C5aR, an important axis in complement pathway, which causes the difference capacity of the dissemination of CTCs between HCC patients. The influence of C5a/C5aR axis on recurrence and HCC cell functions was also explored. Methods: Expression microarray analysis was carried out to identify key molecule that cause the difference of CTC enumeration. Clinical significance of the key gene C5aR was evaluated by immunohistochemistry in 187 resectable HCC patients with CTC detection from March 2011 to October 2014. The function of C5a/C5aR axis to enhance the dissemination capacity of CTCs was confirmed first in HCC cell line and than validated in a mouse model. CTCs isolated from the animal circulation were identified by immunostaining for human EpCAM and nuclear counterstaining of red blood cell-lysed blood. Results: Analysis of 187 HCC patients undergoing curative resection showed that C5aR high expression patients were prone to developing vascular invasion, suffering higher AFP level as well as higher percentage of recurrence and death. Further, C5aR expression was also positive correlated with CTC number in HCC patients. In vitro, we observed that cell migration, invasive, proliferation, anti-apoptosis ability and EMT could be greatly inhibited after C5aR knockdown. Opposite results could be observed when C5aR is overexpressed. Further exploration indicated that C5a/C5aR axis could upregulate the expression of INHBA/Activin, and induce phosphorylation of smad2/3 which maintains the mesenchymal phenotype in HCC. Inhibition of the C5a/C5aR signal pathway could decrease circulating capacities of tumor cells and inhibit their colonization to distal organs such as lung in mouse model. Conclusions: Our research elucidated a new C5a/C5aR targeted INHBA-p-smad2/3-EMT/MMP axis to regulate the dissemination of CTC in HCC patients. And these molecules could be novel therapeutic targets for inhibiting the metastasis of tumor cell in the futures.

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