Circulating Tumor Cells: Diagnostic and Therapeutic Applications

Lin, Eric; Cao, Thong M.; Nagrath, Sunitha; King, Michael R.

doi:10.1146/annurev-bioeng-062117-120947

Cited by 86 publications

(68 citation statements)

References 146 publications

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“…Metastasis is a common cause of death in patients with colorectal cancer (CRC) [1]. Moreover, circulating tumour cells (CTCs) are closely related to tumour metastasis and have become an important biomarker in predicting recurrence and mortality [2]. CTCs survival, and the subsequent adhesion, extravasation, and colonisation of these cells are critical determinants of tumour metastasis [3].…”

Section: Introductionmentioning

confidence: 99%

Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation

Huang

et al. 2020

J Exp Clin Cancer Res

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Background: Metastasis and recurrence, wherein circulating tumour cells (CTCs) play an important role, are the leading causes of death in colorectal cancer (CRC). Metastasis-initiating CTCs manage to maintain intravascular survival under anoikis, immune attack, and importantly shear stress; however, the underlying mechanisms remain poorly understood. Methods: In view of the scarcity of CTCs in the bloodstream, suspended colorectal cancer cells were flowed into the cyclic laminar shear stress (LSS) according to previous studies. Then, we detected these suspended cells with a CK8+/CD45−/DAPI+ phenotype and named them mimic circulating tumour cells (m-CTCs) for subsequent CTCs related researches. Quantitative polymerase chain reaction, western blotting, and immunofluorescence were utilised to analyse gene expression change of m-CTCs sensitive to LSS stimulation. Additionally, we examined atonal bHLH transcription factor 8 (ATOH8) expressions in CTCs among 156 CRC patients and mice by fluorescence in situ hybridisation and flow cytometry. The pro-metabolic and pro-survival functions of ATOH8 were determined by glycolysis assay, live/dead cell vitality assay, anoikis assay, and immunohistochemistry. Further, the concrete up-anddown mechanisms of m-CTC survival promotion by ATOH8 were explored. Results: The m-CTCs actively responded to LSS by triggering the expression of ATOH8, a fluid mechanosensor, with executive roles in intravascular survival and metabolism plasticity. Specifically, ATOH8 was upregulated via activation of VEGFR2/AKT signalling pathway mediated by LSS induced VEGF release. ATOH8 then transcriptionally activated HK2-mediated glycolysis, thus promoting the intravascular survival of colorectal cancer cells in the circulation. Conclusions:This study elucidates a novel mechanism that an LSS triggered VEGF-VEGFR2-AKT-ATOH8 signal axis mediates m-CTCs survival, thus providing a potential target for the prevention and treatment of hematogenous metastasis in CRC.

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Section: Introductionmentioning

confidence: 99%

Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation

Huang

et al. 2020

J Exp Clin Cancer Res

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“…During metastasis formation, the overall natural killer (NK) cell count is increased. CTCs can modulate NK cell anti-tumor activity through production of inhibitory cytokines (e.g., IL-1β, IL-8, IL-10, and prostaglandin E2) that block the NK cell immunoglobulin receptors (KIRs) [2,3] (Figure 3a). Toll-like receptors (TLRs), which are expressed on macrophages and dendritic cells (DCs), can activate NK cell cytolytic killing [67].…”

Section: Ctcs Escape the Innate Immune System Responsementioning

confidence: 99%

“…Finally, hypoxia stress signals ensure CTC survival through activation of autophagy to provide the nutrients (e.g., amino acid, ATP, fatty acid) required for cell metabolism [27]. Immune cells express TNF-related apoptosis-inducing ligand (TRAIL) that binds to the tumor cell membrane death receptors 4/5 (DR4/5) and induces the extrinsic caspase-dependent apoptosis signaling pathway in tumor cells [3,100]. However, autophagy induces DR4/5 endocytosis on CTCs surface, resulting in their degradation and resistance to TRAIL-mediated apoptosis [27].…”

Section: Ctcs Induce Resistance To Chemotherapymentioning

confidence: 99%

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The Role of Circulating Tumor Cells in the Metastatic Cascade: Biology, Technical Challenges, and Clinical Relevance

Dianat‐Moghadam

Azizi

Eslami-S

et al. 2020

Cancers

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Metastases and cancer recurrence are the main causes of cancer death. Circulating Tumor Cells (CTCs) and disseminated tumor cells are the drivers of cancer cell dissemination. The assessment of CTCs’ clinical role in early metastasis prediction, diagnosis, and treatment requires more information about their biology, their roles in cancer dormancy, and immune evasion as well as in therapy resistance. Indeed, CTC functional and biochemical phenotypes have been only partially characterized using murine metastasis models and liquid biopsy in human patients. CTC detection, characterization, and enumeration represent a promising tool for tailoring the management of each patient with cancer. The comprehensive understanding of CTCs will provide more opportunities to determine their clinical utility. This review provides much-needed insights into this dynamic field of translational cancer research.

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“…Additionally, the enrichment and viable CTCs culture from blood of cancer patients will create many opportunities for the development of new anti-cancer drugs for Future therapeutic goals [13]. Isolation and cell counting are also required to monitor post-treatment in many types of cancer therapy [14].…”

Section: Introductionmentioning

confidence: 99%

Design and Experimental Investigation of a Novel Spiral Microfluidic Chip to Separate Wide Size Range of Micro-Particles

Tabatabaei

Targhi

2020

Preprint

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Isolation of microparticles and biological cells on microfluidic chips has received considerable attention due to their applications in numerous areas such as medical and engineering fields. Microparticles separation are of great importance in bioassays owing to the need for a smaller sample and device size, and lower manufacturing costs. In this study, we first explain the concepts of separation and microfluidic science along with their applications in the medical sciences, and then, a conceptual design of a novel inertial microfluidic system is proposed and analyzed. The PDMS spiral microfluidic device was fabricated, and its effects on the separation of particles with sizes similar to biological particles were experimentally analyzed. This separation technique can be used in the process of separating cancer cells from the normal ones in the blood samples. These components required for testing were selected, assembled, and finally, a very affordable microfluidic kit was provided. Different experiments were designed, and the results were analyzed using appropriate software and methods. Separator system tests with polydisperse hollow glass particles (diameter 2–20 µm), and monodisperse Polystyrene particles (diameter 5,15 µm), and the results exhibit an acceptable chip performance with 86 percent of efficiency for both monodisperse particles and polydisperse particles. The microchannel collects particles with an average diameter of 15.8 µm, 9.4 µm, and 5.9 µm at the Proposed reservoirs. This chip can be integrated into a more extensive point-of-care diagnostic system to test blood samples.

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Circulating Tumor Cells: Diagnostic and Therapeutic Applications

Cited by 86 publications

References 146 publications

Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation

Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation

The Role of Circulating Tumor Cells in the Metastatic Cascade: Biology, Technical Challenges, and Clinical Relevance

Design and Experimental Investigation of a Novel Spiral Microfluidic Chip to Separate Wide Size Range of Micro-Particles

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