RRC ID 63557
Author Yamazaki M, Maruyama S, Abé T, Tsuneki M, Kato H, Izumi K, Tanuma JI, Cheng J, Saku T.
Title Rac1-dependent phagocytosis of apoptotic cells by oral squamous cell carcinoma cells: A possible driving force for tumor progression.
Journal Exp Cell Res
Abstract Apoptotic cell death frequently occurs in human cancer tissues including oral squamous cell carcinoma (SCC), wherein apoptotic tumor cells are phagocytosed not only by macrophages but also by neighboring tumor cells. We previously reported that the engulfment of apoptotic SCC cells by neighboring SCC cells frequently occurs at the invading front. Therefore, we hypothesized that the phagocytosis of these apoptotic cells by tumor cells contributes to disease progression. Herein, using cultured oral SCC cells, we aimed to confirm whether tumor cells actually phagocytose apoptotic cells and to examine whether cellular activities are regulated by the phagocytosis of apoptotic cells. Co-culture experiments showed that living cells could ingest apoptotic cells into phagolysosomes. NSC23766, an inhibitor of Rac1, which is a key regulator of phagocytic cup formation in professional phagocytes, dramatically suppressed the phagocytosis of apoptotic cells by living cells. Additionally, cell migration and the secretion of DKK1, a tumor-promoting protein, were enhanced by co-culture with apoptotic cells, whereas NSC23766 inhibited these effects. These results show that tumor cells can actively phagocytose apoptotic neighbors in a Rac1-dependent manner and that such activity increases their migration. The regulation of apoptotic cell phagocytosis thus represents new directions for therapeutic intervention for oral cancer.
Volume 392(1)
Pages 112013
Published 2020-7-1
DOI 10.1016/j.yexcr.2020.112013
PII S0014-4827(20)30235-4
PMID 32320683
MeSH Aminoquinolines / pharmacology Apoptosis / drug effects Apoptosis / genetics* Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / pathology* Cell Movement / drug effects Cell Movement / genetics Cells, Cultured Disease Progression Humans Macrophages / drug effects Macrophages / metabolism Macrophages / pathology Mouth Neoplasms / genetics Mouth Neoplasms / pathology* Phagocytes / drug effects Phagocytes / physiology Phagocytosis / drug effects Phagocytosis / genetics* Phagosomes / drug effects Phagosomes / metabolism Phagosomes / pathology Pyrimidines / pharmacology rac1 GTP-Binding Protein / antagonists & inhibitors rac1 GTP-Binding Protein / physiology*
IF 3.383
Human and Animal Cells Ca9-22(RCB1976) SAS(RCB1974)