scholarly journals Circulating Tumor Cells Develop Resistance to TRAIL-Induced Apoptosis Through Autophagic Removal of Death Receptor 5: Evidence from an In Vitro Model

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 94 ◽  
Author(s):  
Julianne Twomey ◽  
Baolin Zhang
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Immune Surveillance ◽  
Death Receptor ◽  
Metastatic Potential ◽  
Breast Cancer Cell Lines ◽  
Autophagic Flux ◽  
Death Receptor 5 ◽  
Molecular Features

Circulating tumor cells (CTCs) in the peripheral blood are the precursors to distant metastasis but the underlying mechanisms are poorly understood. This study aims at understanding the molecular features within CTCs, in relation to their metastatic potential. Using in vitro CTC models, in which breast cancer cell lines were cultured in non-adherent conditions simulating the microenvironment in the blood stream, we found that the suspension culture resulted in resistance to TNF-related apoptosis inducing ligand (TRAIL)-mediated cell death. Such a resistance was directly correlated with a reduction in surface and total levels of DR5 protein. In the non-adherent state, the cells underwent a rapid autophagic flux, characterized by an accumulation of autophagosome organelles. Notably, DR5 was translocated to the autophagosomes and underwent a lysosomal degradation. Our data suggest that CTCs may evade the TNF cytokine-mediated immune surveillance through a downregulation of the death receptor (DR) expression. The data warrants further studies in cancer patients to find the status of DRs and other molecular features within primary CTCs, in relation to disease progression or chemoresistance.

scholarly journals Circulating Tumor Cells Develop Resistance to TRAIL-Induced Apoptosis through Autophagic Removal of Death Receptor 5: Evidence from an In Vitro Model

2018 ◽  
Author(s):  
Julianne D. Twomey ◽  
Baolin Zhang
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Immune Surveillance ◽  
Death Receptor ◽  
Metastatic Potential ◽  
Breast Cancer Cell Lines ◽  
Autophagic Flux ◽  
Death Receptor 5 ◽  
Molecular Features

Circulating tumor cells (CTCs) in the peripheral blood are the precursors to distant metastasis but the underlying mechanisms are poorly understood.  This study aims at understanding the molecular features within CTCs in relation to their metastatic potential.  Using in vitro CTC models, in which breast cancer cell lines are cultured in non-adherent conditions simulating the microenvironment in the blood stream, we found that suspension culture resulted in resistance to TNF-related apoptosis inducing ligand (TRAIL)-mediated cell death. Such a resistance was directly correlated with a reduction in surface and total levels of DR5 protein. In the non-adherent state, cells underwent rapid autophagic flux characterized by an accumulation of autophagosome organelles. Notably, DR5 was translocated to autophagosomes and underwent lysosomal degradation.  Our data suggest that CTCs may evade TNF cytokine mediated immune surveillance through downregulation of DR expression. The data warrants further studies in cancer patients to find the status of DRs and other molecular features within primary CTCs in relation to disease progression or chemoresistance.

scholarly journals Mitotic arrest affects clustering of tumor cells

2021 ◽  
Author(s):  
Julia Bonnet ◽  
Lise Rigal ◽  
Odile Mondesert ◽  
Renaud Morin ◽  
Gaelle Corsaut ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Cell Aggregation ◽  
Metastatic Potential ◽  
Mitotic Arrest ◽  
Chemotherapeutic Agents ◽  
The Impact ◽  
Mcf 7

Abstract Background Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. Results In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. Conclusions Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.

scholarly journals Mitotic arrest affects clustering of tumor cells

Cell Division ◽  
2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Julia Bonnet ◽  
Lise Rigal ◽  
Odile Mondesert ◽  
Renaud Morin ◽  
Gaëlle Corsaut ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Cell Aggregation ◽  
Metastatic Potential ◽  
Mitotic Arrest ◽  
Vitro Assay ◽  
The Impact ◽  
Mcf 7

Abstract Background Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. Results In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. Conclusions Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.

scholarly journals Mitotic arrest affects clustering of tumor cells

2020 ◽  
Author(s):  
Julia Bonnet ◽  
Lise Rigal ◽  
Odile Mondesert ◽  
Renaud Morin ◽  
Gaelle Corsaut ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Cell Aggregation ◽  
Metastatic Potential ◽  
Mitotic Arrest ◽  
Vitro Assay ◽  
The Impact ◽  
Mcf 7

Abstract BackgroundCancer cell aggregation is a key process involved in the formation of tumor cells clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate the number of CTCs or the size of CTC clusters.ResultsIn this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we found that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly with strongly reduced cohesion. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact.ConclusionsAltogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.

scholarly journals Mitotic arrest affects clustering of tumor cells

2020 ◽  
Author(s):  
Julia Bonnet ◽  
Lise Rigal ◽  
Odile Mondesert ◽  
Renaud Morin ◽  
Gaelle Corsaut ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Cell Aggregation ◽  
Metastatic Potential ◽  
Mitotic Arrest ◽  
Chemotherapeutic Agents ◽  
The Impact ◽  
Mcf 7

Abstract BackgroundCancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters.ResultsIn this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact.ConclusionsAltogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.

scholarly journals Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds

2020 ◽  
Vol 21 (5) ◽  
pp. 1696 ◽  
Author(s):  
Maxim E. Menyailo ◽  
Maria S. Tretyakova ◽  
Evgeny V. Denisov
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Potential ◽  
Critical Issue ◽  
In Vivo Studies ◽  
Multistage Process ◽  
Metastatic Cascade

Metastasis being the main cause of breast cancer (BC) mortality represents the complex and multistage process. The entrance of tumor cells into the blood vessels and the appearance of circulating tumor cells (CTCs) seeding and colonizing distant tissues and organs are one of the key stages in the metastatic cascade. Like the primary tumor, CTCs are extremely heterogeneous and presented by clusters and individual cells which consist of phenotypically and genetically distinct subpopulations. However, among this diversity, only a small number of CTCs is able to survive in the bloodstream and to form metastases. The identification of the metastasis-initiating CTCs is believed to be a critical issue in developing therapeutic strategies against metastatic disease. In this review, we summarize the available literature addressing morphological, phenotypic and genetic heterogeneity of CTCs and the molecular makeup of specific subpopulations associated with BC metastasis. Special attention is paid to the need for in vitro and in vivo studies to confirm the tumorigenic and metastatic potential of metastasis-associating CTCs. Finally, we consider treatment approaches that could be effective to eradicate metastatic CTCs and to prevent metastasis.

Sign in / Sign up

Export Citation Format

Share Document