Magnetic Chip Based Extracorporeal Circulation: A New Tool for Circulating Tumor Cell in Vivo Detection

Abstract BACKGROUND: Pediatric Neuroepithelial Tumors (NT) are one of the most prevalent diseases among children. Developing a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function is very important. Circulating tumor cell (CTC) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTC separation target, an cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposomes (IMLs). The validation and efficiency of this system in capturing CTCs for NT were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed. RESULTS: Our data show that CTCs can be successfully isolated from CSF and blood samples from 29 children with NT. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTC was consistant with tumor tissue. CONCLUSIONS: GFAP-IML isolation of CTCs, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique can be clinically significant in diagnosis and efficacy assessments of pediatric NT.

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Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

Cancers ◽

10.3390/cancers5041691 ◽

2013 ◽

Vol 5 (4) ◽

pp. 1691-1738 ◽

Cited By ~ 59

Author(s):

Ekaterina Galanzha ◽

Vladimir Zharov

Keyword(s):

Flow Cytometry ◽

Tumor Cell ◽

Ex Vivo ◽

Circulating Tumor Cell ◽

Cell Detection ◽

Tumor Cell Detection

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PELP1/SRC-3-dependent regulation of metabolic kinases drives therapy resistant ER+ breast cancer

10.1101/2020.08.07.238550 ◽

2020 ◽

Author(s):

Thu H. Truong ◽

Elizabeth A. Benner ◽

Kyla M. Hagen ◽

Nuri A. Temiz ◽

Carlos Perez Kerkvliet ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Cell ◽

Protein Interactions ◽

Target Genes ◽

Chemotherapy Resistance ◽

Metastatic Breast ◽

Circulating Tumor Cell ◽

Minority Population ◽

Contributing Factors

ABSTRACTRecurrence of metastatic breast cancer stemming from acquired endocrine and chemotherapy resistance remains a health burden for women with luminal (ER+) breast cancer. Disseminated ER+ tumor cells can remain viable but quiescent for years to decades. Contributing factors to metastatic spread include the maintenance and expansion of breast cancer stem cells (CSCs). Breast CSCs frequently exist as a minority population in therapy resistant tumors. In this study, we show that cytoplasmic complexes composed of steroid receptor (SR) co-activators, PELP1 and SRC-3, modulate breast CSC expansion through upregulation of the HIF-activated metabolic target genes PFKFB3 and PFKFB4. Seahorse metabolic assays demonstrated that cytoplasmic PELP1 influences cellular metabolism by increasing both glycolysis and mitochondrial respiration. PELP1 interacts with PFKFB3 and PFKFB4 proteins, and inhibition of PFKFB3 and PFKFB4 kinase activity blocks PELP1-induced tumorspheres and protein-protein interactions with SRC-3. PFKFB4 knockdown inhibited in vivo emergence of circulating tumor cell (CTC) populations in mammary intraductal (MIND) models. Application of PFKFB inhibitors in combination with ER targeted therapies blocked tumorsphere formation in multiple models of advanced breast cancer, including tamoxifen (TamR) and paclitaxel (TaxR) resistant models and ER+ patient-derived organoids (PDxO). Together, our data suggest that PELP1, SRC-3, and PFKFBs cooperate to drive ER+ tumor cell populations that include CSCs and CTCs.SignificanceIdentifying non-ER pharmacological targets offers a useful approach to blocking metastatic escape from standard of care ER/estrogen (E2)-targeted strategies to overcome endocrine and chemotherapy resistance.

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Visualizing Interactions of Circulating Tumor Cell and Dendritic Cell in the Blood Circulation Using In Vivo Imaging Flow Cytometry

IEEE Transactions on Biomedical Engineering ◽

10.1109/tbme.2019.2891068 ◽

2019 ◽

Vol 66 (9) ◽

pp. 2521-2526 ◽

Cited By ~ 3

Author(s):

Dan Wei ◽

Xuejiao Zeng ◽

Zhangru Yang ◽

Quanyu Zhou ◽

Xiaofu Weng ◽

...

Keyword(s):

Flow Cytometry ◽

Dendritic Cell ◽

Tumor Cell ◽

In Vivo Imaging ◽

Blood Circulation ◽

Circulating Tumor Cell ◽

Imaging Flow Cytometry

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In Vivo Monitoring of Rare Circulating Tumor Cell and Cluster Dissemination in a Multiple Myeloma Xenograft Model

10.1101/516641 ◽

2019 ◽

Cited By ~ 2

Author(s):

Roshani Patil ◽

Xuefei Tan ◽

Peter Bartosik ◽

Alexandre Detappe ◽

Judith Runnels ◽

...

Keyword(s):

Multiple Myeloma ◽

Tumor Cell ◽

Fluorescent Protein ◽

Xenograft Model ◽

Circulating Tumor Cell ◽

Hematogenous Metastasis ◽

Circulating Cells ◽

Green Fluorescent ◽

First Time

AbstractWe recently developed ‘Diffuse in vivo Flow Cytometry’ (DiFC), a new pre-clinical research tool for enumerating extremely rare fluorescently-labeled circulating cells directly in vivo. In this paper, we developed a green fluorescent protein (GFP) compatible version of DiFC, and used it to non-invasively monitor the circulating tumor cell (CTC) burden over time in a multiple myeloma disseminated xenograft model. We show that DiFC allowed counting of CTCs at estimated concentrations below 1 cell per mL in peripheral blood with a negligible false alarm rate. DiFC also revealed the presence of CTC clusters in circulation to our knowledge for the first time in this model, and allowed us to calculate their size, kinetics, and frequency of shedding. We anticipate that the unique capabilities of DiFC will have many applications in the study of hematogenous metastasis, and as a powerful complementary methodology to liquid biopsy assays.

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