論文

査読有り 国際誌
2020年4月19日

Rac1-dependent phagocytosis of apoptotic cells by oral squamous cell carcinoma cells: A possible driving force for tumor progression.

Experimental cell research
  • Manabu Yamazaki
  • ,
  • Satoshi Maruyama
  • ,
  • Tatsuya Abé
  • ,
  • Masayuki Tsuneki
  • ,
  • Hiroko Kato
  • ,
  • Kenji Izumi
  • ,
  • Jun-Ichi Tanuma
  • ,
  • Jun Cheng
  • ,
  • Takashi Saku

開始ページ
112013
終了ページ
112013
記述言語
英語
掲載種別
DOI
10.1016/j.yexcr.2020.112013

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.

リンク情報
DOI
https://doi.org/10.1016/j.yexcr.2020.112013
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32320683
ID情報
  • DOI : 10.1016/j.yexcr.2020.112013
  • PubMed ID : 32320683

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