We are analyzing https://link.springer.com/article/10.1186/s13062-016-0135-4.

Title:
Stem-like features of cancer cells on their way to metastasis | Biology Direct
Description:
Abstract More than 90 % of cancer-related deaths are due to the development of a systemic metastatic disease. Clearly, much remains to be understood about the biological principles that govern human cancer metastasis, aiming at the ambitious objective to decrease metastasis-related mortality in patients. For many years, research on metastasis has been conducted in great part on experimental mouse models, mainly because of the difficulties in sampling, longitudinal studies, and molecular interrogation of a human metastatic disease. However, recently, extraordinary advances in microfluidic technologies are allowing the isolation and characterization of human circulating tumor cells (CTCs) that escaped a primary tumor mass and are in the process of seeding a distant metastasis. Analysis of human CTCs has now revealed important features of cancer metastasis, such as the high metastatic potential of CTC-clusters compared to single CTCs, the dynamic expression of epithelial and mesenchymal markers on CTCs during treatment, and the possibility to culture CTCs from patients for a real-time and individualized testing of drug susceptibility. Nevertheless, several aspects of CTC biology remain unsolved, such as the characterization of the stem-like cell population among human CTCs. Here, we focus on describing the latest findings in the CTC field, and discuss them in the context of cancer stem cell biology. Defining the molecular features of those few metastasis-initiating, stem-like CTCs holds the exceptional promise to develop metastasis-tailored therapies for patients with cancer. Reviewers This article was reviewed by Elisa Cimetta, Luca Pellegrini and Sirio Dupont (nominated by LP).
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Keywords {🔍}

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Topics {✒️}

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Questions {❓}

4, from line 23 on): could the authors comment on the potential effects (membrane damages, pathways activation, etc) elicited by shear forces on the exposed cells?
8, from line 41 on): could this be linked to the fact that CTCs clusters appear to be enriched in stem-like cells?
Can certain genetic or epigenetic signatures promote stem-like features and are these signatures enriched in a subset of CTCs?
Circulating tumor cell enumeration by the cell search system: the clinician’s guide to breast cancer treatment?
How then these different aspects would merge in the case of CTC clusters?
Minor issues: Page8, line 58: “we shown” should maybe be “were shown”?
Page 4, line 18: clarify if this is the size of single or clustered CTC?
Page 5: What can we learn, or at least estimate, on human disease from the CTC half-life in mice and the observed CTC frequencies in human patients?
Page 5: was the correlation between cluster CTC and malignancy observed in human cancer patients corrected for the grade/burden of the primary tumor?
Please also remember that LGR5 was isolated as a normal stem cell marker based on the hypothetical assumption that cancer cells recapitulate traits of the physiologic stem cell (VanDeWetering and Clevers original paper), but how many of the physiological stem cell markers identified thereafter do follow this rule and are also found in cancer stem cell populations?
To which extent a homogeneous system like MDA-LM2 is informative on heterogeneous cancer populations containing both stem and non-stem cancer cells?

Schema {🗺️}

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      headline:Stem-like features of cancer cells on their way to metastasis
      description:More than 90 % of cancer-related deaths are due to the development of a systemic metastatic disease. Clearly, much remains to be understood about the biological principles that govern human cancer metastasis, aiming at the ambitious objective to decrease metastasis-related mortality in patients. For many years, research on metastasis has been conducted in great part on experimental mouse models, mainly because of the difficulties in sampling, longitudinal studies, and molecular interrogation of a human metastatic disease. However, recently, extraordinary advances in microfluidic technologies are allowing the isolation and characterization of human circulating tumor cells (CTCs) that escaped a primary tumor mass and are in the process of seeding a distant metastasis. Analysis of human CTCs has now revealed important features of cancer metastasis, such as the high metastatic potential of CTC-clusters compared to single CTCs, the dynamic expression of epithelial and mesenchymal markers on CTCs during treatment, and the possibility to culture CTCs from patients for a real-time and individualized testing of drug susceptibility. Nevertheless, several aspects of CTC biology remain unsolved, such as the characterization of the stem-like cell population among human CTCs. Here, we focus on describing the latest findings in the CTC field, and discuss them in the context of cancer stem cell biology. Defining the molecular features of those few metastasis-initiating, stem-like CTCs holds the exceptional promise to develop metastasis-tailored therapies for patients with cancer. This article was reviewed by Elisa Cimetta, Luca Pellegrini and Sirio Dupont (nominated by LP).
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