Biphasic Increases of Cell Surface Calreticulin Following Treatment with Mitoxantrone
| Autor: | Kojiro Matsumoto, Kenichi Suzuki, Koji Higai, Yutaro Azuma, Shusuke Tada |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
genetic structures Calnexin Pharmaceutical Science Antineoplastic Agents Apoptosis Caspase 8 Endoplasmic Reticulum 03 medical and health sciences 0302 clinical medicine Phagocytosis Neoplasms Humans Caspase Pharmacology biology Chemistry Endoplasmic reticulum fungi Cell Membrane Calpain General Medicine Endoplasmic Reticulum Stress Cell biology 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Unfolded protein response biology.protein Mitoxantrone Calreticulin Reactive Oxygen Species HT29 Cells |
| Zdroj: | Biologicalpharmaceutical bulletin. 43(10) |
| ISSN: | 1347-5215 |
| Popis: | Calreticulin (CRT) and calnexin (CNX), homologous major chaperones in the endoplasmic reticulum (ER), are known to translocate to the cell surface in response to chemotherapeutic agents, such as mitoxantrone (MIT), and cellular stresses, including apoptosis. Cell surface CRT (ecto-CRT) is relevant to the phagocytic uptake of cancer cells and dying cells, and pre-apoptotic exposure of CRT has been reported to result in enhanced immunogenicity of dying tumor cells, serving as a damage-associated molecular pattern (DAMP). In this study, HT-29 cells were treated with MIT to induce ER stress, and ecto-CRT and cell surface CNX were quantified by flow cytometry in the absence or presence of caspase inhibitors, a calpain inhibitor, or a scavenger of reactive oxygen species. The biphasic (early transient and late sustained) increase of ecto-CRT on HT-29 cells was observed after treatment with MIT. We confirmed that the early increase in ecto-CRT after 4 h of MIT treatment was not related to apoptosis, whereas the increase of ecto-CRT, as well as that of cell-surface CNX, during the later stage of treatment was caspase dependent and related to apoptosis. In addition, our results suggested that the early peak of ecto-CRT was mediated by activation of caspase 8 by ER stress. Thus, the physiological significance of the late increases in cell-surface CRT and/or CNX might be considered an "eat-me signal'' for the removal of dead cells by phagocytosis, while the early increase in ecto-CRT caused by ER stress might enhance the immunogenicity of stressed tumor cells. |
| Databáze: | OpenAIRE |
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