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Phosphatidylserine-mediated phagocytosis of anticancer drug-treated cells by macrophages
1Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-0934, Japan.
Abstract:
Apoptotic cells are rapidly phagocytosed and eliminated from the organism. Although cancer cells apoptose when treated with anticancer drugs, how those cells are recognized by phagocytic cells has remained unclear. The human leukemia cell line Jurkat was cultured with doxorubicin or bufalin and induced to undergo apoptosis accompanied by phosphatidylserine externalization. When apoptotic Jurkat cells were mixed with mouse peritoneal macrophages, efficient phagocytosis was observed. Apoptosis and phagocytosis of Jurkat cells were both inhibited by Z-VAD-FMK, and phagocytosis was significantly reduced in the presence of phosphatidylserine-containing liposomes. These results suggest that anticancer drugs induce apoptosis-dependent and phosphatidylserine-mediated phagocytosis in cancer cells.
Insights
Anticancer drugs trigger cancer cell apoptosis, leading to recognition and phagocytosis by immune cells. This process relies on phosphatidylserine externalization, a key signal for efficient clearance.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Apoptotic cells are typically cleared rapidly by phagocytes.
- The mechanisms by which phagocytic cells recognize and engulf cancer cells undergoing drug-induced apoptosis are not fully understood.
Purpose of the Study:
- To investigate the recognition and phagocytosis of cancer cells undergoing apoptosis induced by anticancer drugs.
- To elucidate the role of phosphatidylserine externalization in this process.
Main Methods:
- Human leukemia (Jurkat) cells were treated with doxorubicin or bufalin to induce apoptosis.
- Apoptotic Jurkat cells were co-cultured with mouse peritoneal macrophages.
- The effects of Z-VAD-FMK (a caspase inhibitor) and phosphatidylserine-containing liposomes on phagocytosis were assessed.
Main Results:
- Anticancer drug treatment induced apoptosis and phosphatidylserine externalization in Jurkat cells.
- Efficient phagocytosis of apoptotic Jurkat cells by macrophages was observed.
- Both apoptosis and phagocytosis were inhibited by Z-VAD-FMK.
- Phagocytosis was significantly reduced when phosphatidylserine-containing liposomes were present.
Conclusions:
- Anticancer drugs induce apoptosis in cancer cells.
- This apoptosis involves externalization of phosphatidylserine.
- Phosphatidylserine serves as a signal for phagocytosis of these cancer cells by macrophages.
- The findings suggest a mechanism for the clearance of drug-treated cancer cells.