Evaluation of a developmental hierarchy for breast cancer cells to assess risk-based patient selection for targeted treatment

Bliss, Sarah A.; Paul, Sunirmal; Pobiarzyn, Piotr W.; Ayer, Seda; Sinha, Garima; Pant, Saumya; Hilton, Holly; Sharma, Neha; Cunha, Maria Fernanda; Engelberth, Daniel J.; Greco, Steven J.; Bryan, Margarette; Kucia, Magda; Kakar, Sham S.; Ratajczak, Mariusz Z.; Rameshwar, Pranela

doi:10.1038/s41598-017-18834-5

Cited by 25 publications

(20 citation statements)

References 43 publications

(59 reference statements)

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“…We then tested the effects of imatinib and ponatinib on cells endowed with ALDH activity using K562, LAMA-84, and LAMA-84R cells that, differently from KCL22 cells, show high levels of ALDH activity ( Supplementary Fig S2a [see ESM]; Table 2), in agreement with data reported previously for K562 cells [63,64]. Both drugs similarly reduced the percentages (Fig.…”

Section: Effects Of Imatinib and Ponatinib On Stem Cell Markers In CMsupporting

confidence: 83%

In Vitro Comparison of the Effects of Imatinib and Ponatinib on Chronic Myeloid Leukemia Progenitor/Stem Cell Features

et al. 2020

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Background The development of molecularly tailored therapeutic agents such as the BCR/ABL-active tyrosine kinase inhibitors (TKi) resulted in an excellent treatment option for chronic myeloid leukemia (CML) patients. However, following TKi discontinuation, disease relapses in 40-60% of patients, an occurrence very likely due to the persistence of leukemic stem cells that are scarcely sensitive to TKi. Nevertheless, TKi are still the only current treatment option for CML patients. Objective The aim of this study was to compare the effects of TKi belonging to different generations, imatinib and ponatinib (first and third generation, respectively), on progenitor/stem cell expansion potential and markers. Patients and Methods We used stabilized CML cell lines (KCL22, K562 and LAMA-84 cells), taking advantage of the previous demonstration of ours that cell lines contain cell subsets endowed with progenitor/stem cell properties. Primary cells explanted from CML patients were also used. The effects of TKi on the expression of stem cell related genes were compared by quantitative PCR. Flow cytometry was performed to evaluate aldehyde-dehydrogenase (ALDH) activity and the expression of cluster of differentiation (CD) cell surface hematopoietic stem cell markers. Progenitor/stem cell potential was estimated by serial colony formation ability (CFA) assay. Results Ponatinib was more effective than imatinib for the reduction of cells with ALDH activity and progenitor/stem cell potential of CML patient-derived cells and cell lines. Furthermore, ponatinib was more effective than imatinib in reducing the percentage of CD26-expressing cells in primary CML cells, whereas imatinib and ponatinib showed similar efficacy on KCL22 cells. Both drugs strongly upregulated NANOG and SOX2 in CML cell lines, but in KCL22 cells this upregulation was significantly lower with ponatinib than with imatinib, an outcome compatible with a lower level of enrichment of the stem cell compartment upon ponatinib treatment. Conclusion Ponatinib seems to target CML progenitor/stem cells better than imatinib.

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Section: Effects Of Imatinib and Ponatinib On Stem Cell Markers In CMsupporting

confidence: 83%

In Vitro Comparison of the Effects of Imatinib and Ponatinib on Chronic Myeloid Leukemia Progenitor/Stem Cell Features

et al. 2020

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“…To investigate the ALDH1A1 sensing capabilities of AlDeSense in cell culture, we utilized the K562 human chronic myeloid leukemia cell line, which is known to exhibit high overall ALDH activity. 44 We hypothesized that AlDeSense can be used to stratify these cells based on ALDH1A1 activity and that the brightest cells would exhibit CSC markers. First, using flow cytometry analysis, we found that K562 cells stained with AlDeSense are significantly brighter compared to those treated with either AlDeSense with an inhibitor or Ctrl-AlDeSense ( Figures 2 a–c and S8 ).…”

Section: Resultsmentioning

confidence: 99%

Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1

et al. 2018

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Cancer stem cells (CSCs) are progenitor cells that contribute to treatment-resistant phenotypes during relapse. CSCs exist in specific tissue microenvironments that cell cultures and more complex models cannot mimic. Therefore, the development of new approaches that can detect CSCs and report on specific properties (e.g., stem cell plasticity) in their native environment have profound implications for studying CSC biology. Herein, we present AlDeSense, a turn-on fluorescent probe for aldehyde dehydrogenase 1A1 (ALDH1A1) and Ctrl-AlDeSense, a matching nonresponsive reagent. Although ALDH1A1 contributes to the detoxification of reactive aldehydes, it is also associated with stemness and is highly elevated in CSCs. AlDeSense exhibits a 20-fold fluorescent enhancement when treated with ALDH1A1. Moreover, we established that AlDeSense is selective against a panel of common ALDH isoforms and exhibits exquisite chemostability against a collection of biologically relevant species. Through the application of surface marker antibody staining, tumorsphere assays, and assessment of tumorigenicity, we demonstrate that cells exhibiting high AlDeSense signal intensity have properties of CSCs. Using these probes in tandem, we have identified CSCs at the cellular level via flow cytometry and confocal imaging, as well as monitored their states in animal models.

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“…The findings will reveal crucial targets (eg, stemness defect, stemness resurrection, unchecked survival drive, etc.) for assessing risk-based patient selection for receiving a particular medical procedure and developing efficacious targeted treatment for malignant tumors [ 10 , 82 , 112 , 113 ].…”

Section: Discussionmentioning

confidence: 99%

Cancer Stem Cells or Tumor Survival Cells?

Teng

Wang

Kabataş

et al. 2018

Stem Cells and Development

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Research endeavors originally generated stem cell definitions for the purpose of describing normally sustainable developmental and tissue turnover processes in various species, including humans. The notion of investigating cells that possess a vague capacity of “stamm (phylum)” can be traced back to the late 19th century, mainly concentrating on cells that could produce the germline or the entire blood system. Lately, such undertakings have been recapitulated for oncogenesis, tumor growth, and cancer cell resistance to oncolytic therapies. However, due to the complexity and basic life-origin mechanisms comprising the genetic and epigenetic repertoire of the stemness in every developing or growing cell, presently there are ongoing debates regarding the biological essentials of the stem cell-like tumor initiation cells (ie, cancer stem cells; CSCs). This conceptual analysis focuses on the potential pitfalls of extrapolating that CSCs bear major traits of stemness. We propose a novel nomenclature of Tumor Survival Cells (TSCs) to further define tumor cells behaving like CSCs, based on the ruthless and detrimental features of Cancer Cell Survivology that appears fundamentally different from stem cell biology. Hence, precise academic separation of TSCs from all the stem cell-related labels applied to these unique tumor cells may help to improve scientific reasoning and strategies to decode the desperado-like survival behaviors of TSCs to eventually overcome cancer.

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Evaluation of a developmental hierarchy for breast cancer cells to assess risk-based patient selection for targeted treatment

Cited by 25 publications

References 43 publications

In Vitro Comparison of the Effects of Imatinib and Ponatinib on Chronic Myeloid Leukemia Progenitor/Stem Cell Features

In Vitro Comparison of the Effects of Imatinib and Ponatinib on Chronic Myeloid Leukemia Progenitor/Stem Cell Features

Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1

Cancer Stem Cells or Tumor Survival Cells?

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