scholarly journals Lymph-Circulating Tumor Cells show distinct properties to Blood-Circulating Tumor Cells and constitute extraordinary efficient metastatic precursors

2018 ◽  
Author(s):  
Sulma I Mohammed ◽  
Odalys Torres Luquis ◽  
El Wood Walls ◽  
Frank Lloyd
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Expression Profiles ◽  
Parental Cell ◽  
Breast Cancer Metastasis ◽  
Primary Tumors ◽  
Gene And Protein Expression ◽  
Protein Expression Profiles

The molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sentinel lymph nodes (SLNs) are not yet known. We developed an innovative technique that enables the collection of lymph and lymph-circulating tumor cells (LCTCs) en route to the SLN in immunocompetent animal model of breast cancer metastasis. We found that LCTCs and blood circulating tumor cells (BCTCs) as exited the primary tumor shared similar gene and protein expression profiles that were distinct from those of primary tumors and lymph node metastases (LNMs) despite their common parental cell origin. LCTCs but not BCTC exist in clusters, display a hybrid epithelial/mesenchymal phenotype and cancer stem cell-like properties and constitute extraordinarily efficient metastatic precursors. These results demonstrate that tumor cell metastasizing through the lymphatic are different from those spread by the blood circulation. The contribution of these cells to overall peripheral blood CTC is important in cancer therapy. Whether these two types of cells occur in cancer patients remain to be determined.

scholarly journals Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

Micromachines ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 774 ◽  
Author(s):  
Jie Cheng ◽  
Yang Liu ◽  
Yang Zhao ◽  
Lina Zhang ◽  
Lingqian Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Cancer Metastasis ◽  
Human Peripheral Blood ◽  
Microfluidic Devices ◽  
Detection Sensitivity ◽  
Cell Capture ◽  
Primary Tumors ◽  
Downstream Analysis

Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.

scholarly journals Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

2020 ◽  
Vol 21 (5) ◽  
pp. 1671 ◽  
Author(s):  
Anna Fabisiewicz ◽  
Malgorzata Szostakowska-Rodzos ◽  
Anna J. Zaczek ◽  
Ewa A. Grzybowska
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Current Status ◽  
Molecular Profile ◽  
Breast Cancer Patients

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.

scholarly journals Detection of Circulating Tumor Cells in Early-Stage Breast Cancer Metastasis to Axillary Lymph Nodes

2007 ◽  
Vol 13 (14) ◽  
pp. 4105-4110 ◽  
Author(s):  
Taku Nakagawa ◽  
Steve R. Martinez ◽  
Yasufumi Goto ◽  
Kazuo Koyanagi ◽  
Minoru Kitago ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Early Stage ◽  
Breast Cancer Metastasis ◽  
Early Stage Breast Cancer ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph

scholarly journals Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 618 ◽  
Author(s):  
Jeannette Huaman ◽  
Michelle Naidoo ◽  
Xingxing Zang ◽  
Olorunseun O. Ogunwobi
Keyword(s):  
Mouse Model ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Castration Resistant Prostate Cancer ◽  
Good Tool ◽  
Mesenchymal Transition ◽  
Syngeneic Mouse Model

Metastasis is the leading cause of cancer death worldwide. Circulating tumor cells (CTCs) are a critical step in the metastatic cascade and a good tool to study this process. We isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prostate cancer (CRPC). From these models, novel primary tumor and CTC cell lines were established. CTCs exhibited greater migration than primary tumor-derived cells, as well as epithelial-to-mesenchymal transition (EMT), as observed from decreased E-cadherin and increased SLUG and fibronectin expression. Additionally, when fibronectin was knocked down in CTCs, integrin B1 and SLUG were decreased, indicating regulation of these molecules by fibronectin. Investigation of cell surface molecules and secreted cytokines conferring immunomodulatory advantage to CTCs revealed decreased major histocompatibility complex class I (MHCI) expression and decreased endostatin, C-X-C motif chemokine 5 (CXCL5), and proliferin secretion by CTCs. Taken together, these findings indicate that CTCs exhibit distinct characteristics from primary tumor-derived cells. Furthermore, CTCs demonstrate enhanced migration in part through fibronectin regulation of integrin B1 and SLUG. Further study of CTC biology will likely uncover additional important mechanisms of cancer metastasis.

Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer

2015 ◽  
Vol 362 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Wendy Onstenk ◽  
Anieta M. Sieuwerts ◽  
Marleen Weekhout ◽  
Bianca Mostert ◽  
Esther A. Reijm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metastatic Breast ◽  
Primary Tumors

scholarly journals ctcRbase: the gene expression database of circulating tumor cells and microemboli

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Lei Zhao ◽  
Xiaohong Wu ◽  
Tong Li ◽  
Jian Luo ◽  
Dong Dong
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Circulating Tumor Cell ◽  
Gene Signature ◽  
Primary Tumors ◽  
A Genome ◽  
Experimental Validations ◽  
Transcriptomic Changes

Abstract Circulating tumor cells/microemboli (CTCs/CTMs) are malignant cells that depart from cancerous lesions and shed into the bloodstream. Analysis of CTCs can allow the investigation of tumor cell biomarker expression from a non-invasive liquid biopsy. To date, high-throughput technologies have become a powerful tool to provide a genome-wide view of transcriptomic changes associated with CTCs/CTMs. These data provided us much information to understand the tumor heterogeneity, and the underlying molecular mechanism of tumor metastases. Unfortunately, these data have been deposited into various repositories, and a uniform resource for the cancer metastasis is still unavailable. To this end, we integrated previously published transcriptome datasets of CTCs/CTMs and constructed a web-accessible database. The first release of ctcRbase contains 526 CTCs/CTM samples across seven cancer types. The expression of 14 631 mRNAs and 3642 long non-coding RNAs of CTCs/CTMs were included. Experimental validations from the published literature are also included. Since CTCs/CTMs are considered to be precursors of metastases, ctcRbase also collected the expression data of primary tumors and metastases, which allows user to discover a unique ‘circulating tumor cell gene signature’ that is distinct from primary tumor and metastases. An easy-to-use database was constructed to query and browse CTCs/CTMs genes. ctcRbase can be freely accessible at http://www.origin-gene.cn/database/ctcRbase/.

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.

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