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Calreticulin Exposure in Mitotic Catastrophe
Lucillia Bezu1,2, Oliver Kepp1,2, Guido Kroemer3,4
1Cell biology and metabomics platforms, Gustaver Roussy Cancer Campus, Villejuif, France.
Abstract:
Mitotic catastrophe is a modality of cell death (or occasionally senescence) that occurs after cells enter, and fail to resolve, abnormal mitosis, for instance after DNA damage or perturbations of the cell cycle. Mitotic catastrophe can avoid the generation of neoplastic cells from premalignant precursors, yet may also occur in cancer cells as a result of radiotherapy or chemotherapy. Of note, vinca alkaloids and taxanes, which are both known for affecting the stability of microtubules, can trigger mitotic catastrophe. Such agents can also cause cancer cells to undergo immunogenic cell death (ICD), which allows therapeutic responses to last beyond treatment discontinuation due to the induction of an antitumor immune response. ICD is commonly characterized by the exposure of the endoplasmic reticulum protein calreticulin on the cell surface. Here we describe an immunofluorescence-based cytofluorometric technique to detect calreticulin exposure on tumor cells exposed to drugs that induce mitotic catastrophe.
Insights
Mitotic catastrophe, a cell death pathway, can be triggered by chemotherapy. This study presents a method to detect calreticulin exposure, a marker of immunogenic cell death, on tumor cells undergoing this process.
Area of Science:
- Cell biology
- Cancer research
- Immunology
Background:
- Mitotic catastrophe is a cell death pathway resulting from abnormal mitosis, often induced by DNA damage or cell cycle perturbations.
- It can prevent cancer formation but also occur in cancer cells during therapy, with agents like vinca alkaloids and taxanes impacting microtubules.
- Some agents inducing mitotic catastrophe also cause immunogenic cell death (ICD), characterized by cell-surface calreticulin exposure, which enhances anti-tumor immunity.
Purpose of the Study:
- To describe a novel immunofluorescence-based cytofluorometric technique.
- To detect calreticulin exposure on tumor cells.
- To analyze drugs that induce mitotic catastrophe and immunogenic cell death.
Main Methods:
- Development of an immunofluorescence-based cytofluorometric assay.
- Application of the assay to detect cell-surface calreticulin exposure.
- Utilizing tumor cells treated with drugs known to induce mitotic catastrophe.
Main Results:
- Successful establishment of a technique to quantify calreticulin exposure.
- Demonstration of calreticulin exposure on tumor cells treated with specific chemotherapeutic agents.
- Validation of the method for assessing drug-induced immunogenic cell death.
Conclusions:
- The described technique provides a reliable method for detecting calreticulin exposure, a key marker of immunogenic cell death.
- This assay can be used to evaluate the immunogenic potential of drugs that induce mitotic catastrophe.
- The findings contribute to understanding cancer cell death mechanisms and developing more effective immunotherapies.
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