scholarly journals In Vivo Lymphatic Circulating Tumor Cells and Progression of Metastatic Disease

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2866
Author(s):  
Mikyung Han ◽  
Julia Alex Watts ◽  
Azemat Jamshidi-Parsian ◽  
Urooba Nadeem ◽  
Mustafa Sarimollaoglu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
High Sensitivity ◽  
Disease Stage ◽  
Primary Tumors ◽  
Integrative Assessment

The dissemination of circulating tumor cells (CTCs) by lymph fluid is one of the key events in the development of tumor metastasis. However, little progress has been made in studying lymphatic CTCs (L-CTCs). Here, we demonstrate the detection of L-CTCs in preclinical mouse models of melanoma and breast cancer using in vivo high-sensitivity photoacoustic and fluorescent flow cytometry. We discovered that L-CTCs are be detected in pre-metastatic disease stage. The smallest primary tumor that shed L-CTCs was measured as 0.094mm×0.094mm, its volume was calculated as 0.0004 mm3; and its productivity was estimated as 1 L-CTC per 30 minutes. As the disease progressed, primary tumors continued releasing L-CTCs with certain individual dynamics. The integrated assessment of lymph and blood underlined the parallel dissemination of CTCs at all disease stages. However, the analysis of links between L-CTC counts, blood CTC (B-CTC) counts, primary tumor size and metastasis did not reveal statistically significant correlations, likely due to L-CTC heterogeneity. Altogether, our results showed the feasibility of our diagnostic platform using photoacoustic flow cytometry for preclinical L-CTC research with translational potential. Our findings also demonstrated new insights into lymphatic system involvement in CTC dissemination. They help to lay the scientific foundation for the consideration of L-CTCs as prognostic markers of metastasis and to emphasize the integrative assessment of lymph and blood.

scholarly journals In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry

2007 ◽  
Vol 104 (28) ◽  
pp. 11760-11765 ◽  
Author(s):  
W. He ◽  
H. Wang ◽  
L. C. Hartmann ◽  
J.-X. Cheng ◽  
P. S. Low
Keyword(s):  
Flow Cytometry ◽  
Tumor Cells ◽  
Circulating Tumor Cells

A new medical device for in vivo capturing of circulating tumor cells in breast cancer (BC) patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10537-10537
Author(s):  
Dawid Murawa ◽  
Stefanie Herold ◽  
Phillip Sangwook Kim ◽  
Arndt Schmitz ◽  
Thomas Krahn ◽  
...  
Keyword(s):  
Side Effects ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Ex Vivo ◽  
Therapy Monitoring ◽  
Blood Stream ◽  
Disease Stage ◽  
Positive Staining ◽  
The Wire

10537 Background: In BC, the number of circulating tumor cells (CTCs) is discussed as a prognostic and stratification biomarker, and could also reflect treatment efficacy. Currently, CTCs are isolated ex vivo from a small volume of blood. Results from a larger volume of blood are scarce. The aim of the study was to assess a functionalized and structured medical wire (FSMW) for in vivo capturing of CTCs directly from the blood stream of BC patients. Methods: The device was inserted in a cubital vein through a standard cannula for thirty minutes. The interaction of target CTCs with the FSMW was mediated by antibodies directed against the epithelial cell adhesion molecule (EpCAM). To confirm binding of CTCs to the wire, the immunohistochemical positive staining against EpCAM as well as negative staining for CD45 was performed. There were 54 applications of the wire in 42 stage I-IV BC patients (12 double applications). Enumeration data from 37 BC patients with 49 applications (5 failed subsequent analyses) were assessed. CTC counts on 23 devices were directly compared to counts by CellSearch. Results: The device was well tolerated in all 54 applications without side effects. We obtained in vivo isolation of CTCs in 44 of 49 applications to BC patients (89.7 %). The sensitivity was similar for early and late stage BC patients. The median (range) of isolated EpCAM-positive CTCs was 5 (0-515). The CellSearch method reached a sensitivity of 18.5%. In all paired samples the number of CTCs detected with the FSMW was higher or equal to CellSearch, regardless of the disease stage. Linear regression of the data of the double application of the FSMW showed a very good concordance (r2 = 0.97, p<0.0001). Conclusions: Whilst well tolerated without side effects, the CTC detection rate of the FSMW in BC patients was nearly 90 %. CTC detection was obtained in 18.5% by the CellSearch. Double application of FSMWs in the same patient indicates ample precision. This proof of concept study may have important clinical implications, as the device may improve early detection, prognosis and therapy monitoring of BC patients. The molecular analysis of the captured CTCs could become a breakthrough in personalized medicine.

scholarly journals Detection of Apoptotic Circulating Tumor Cells Using in vivo Fluorescence Flow Cytometry

2018 ◽  
Vol 95 (6) ◽  
pp. 664-671 ◽  
Author(s):  
Jacqueline Nolan ◽  
Dmitry A. Nedosekin ◽  
Ekaterina I. Galanzha ◽  
Vladimir P. Zharov
Keyword(s):  
Flow Cytometry ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
In Vivo Fluorescence

scholarly journals Fluorescence Labeling of Circulating Tumor Cells with Folate Receptor Targeted Molecular Probes for Diffuse In Vivo Flow Cytometry

2020 ◽  
Author(s):  
Roshani Patil ◽  
Madduri Srinivasarao ◽  
Mansoor Amiji ◽  
Philip S. Low ◽  
Mark Niedre
Keyword(s):  
Flow Cytometry ◽  
Animal Models ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Folate Receptor ◽  
Molecular Probes ◽  
Cell Surface Receptor

AbstractPurposeWe recently developed a new instrument called ‘diffuse in vivo flow cytometry’ (DiFC) for enumeration of rare fluorescently-labeled circulating tumor cells (CTCs) in small animals without drawing blood samples. Until now, we have used cell lines that express fluorescent proteins, or were pre-labeled with a fluorescent dye ex-vivo. In this work, we investigated the use of two folate receptor (FR)-targeted fluorescence molecular probes for in vivo labeling of FR+ CTCs for DiFC.MethodsWe used EC-17 and Cy5-PEG-FR fluorescent probes. We studied the affinity of these probes for L1210A and KB cancer cells, both of which over-express FR. We tested the labeling specificity in cells in culture in vitro, in whole blood, and in mice in vivo. We also studied detectability of labeled cells with DiFC.ResultsBoth EC-17 and Cy5-PEG-FR probes had high affinity for FR+ CTCs in cell culture in vitro. However, only EC-17 had sufficient specificity for CTCs in whole blood. EC-17 labeled CTCs were also readily detectable in circulation in mice with DiFC.ConclusionsThis work demonstrates the feasibility of labeling CTCs for DiFC with a cell surface receptor targeted probe, greatly expanding the utility of the method for pre-clinical animal models. Because DiFC uses diffuse light, this method could be also used to enumerate CTCs in larger animal models and potentially even in humans.

scholarly journals Platelet microRNAs inhibit primary tumor growth via broad modulation of tumor cell mRNA expression in ectopic pancreatic cancer in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261633
Author(s):  
Jeremy G. T. Wurtzel ◽  
Sophia Lazar ◽  
Sonali Sikder ◽  
Kathy Q. Cai ◽  
Igor Astsaturov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Primary Tumor ◽  
Primary Tumor Growth ◽  
Primary Tumors ◽  
Solid Tumor Growth

We investigated the contributions of platelet microRNAs (miRNAs) to the rate of growth and regulation of gene expression in primary ectopic tumors using mouse models. We previously identified an inhibitory role for platelets in solid tumor growth, mediated by tumor infiltration of platelet microvesicles (microparticles) which are enriched in platelet-derived miRNAs. To investigate the specific roles of platelet miRNAs in tumor growth models, we implanted pancreatic ductal adenocarcinoma cells as a bolus into mice with megakaryocyte-/platelet-specific depletion of mature miRNAs. We observed an ~50% increase in the rate of growth of ectopic primary tumors in these mice compared to controls including at early stages, associated with reduced apoptosis in the tumors, in particular in tumor cells associated with platelet microvesicles—which were depleted of platelet-enriched miRNAs—demonstrating a specific role for platelet miRNAs in modulation of primary tumor growth. Differential expression RNA sequencing of tumor cells isolated from advanced primary tumors revealed a broad cohort of mRNAs modulated in the tumor cells as a function of host platelet miRNAs. Altered genes comprised 548 up-regulated transcripts and 43 down-regulated transcripts, mostly mRNAs altogether spanning a variety of growth signaling pathways–notably pathways related to epithelial-mesenchymal transition—in tumor cells from platelet miRNA-deleted mice compared with those from control mice. Tumors in platelet miRNA-depleted mice showed more sarcomatoid growth and more advanced tumor grade, indicating roles for host platelet miRNAs in tumor plasticity. We further validated increased protein expression of selected genes associated with increased cognate mRNAs in the tumors due to platelet miRNA depletion in the host animals, providing proof of principle of widespread effects of platelet miRNAs on tumor cell functional gene expression in primary tumors in vivo. Together, these data demonstrate that platelet-derived miRNAs modulate solid tumor growth in vivo by broad-spectrum restructuring of the tumor cell transcriptome.

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