Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation
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(2020) 21:79
BMC Molecular and Cell Biology
RESEARCH ARTICLE
Open Access
Role of tumor cell senescence in nonprofessional phagocytosis and cell-in-cell structure formation Dorian Gottwald1†, Florian Putz1†, Nora Hohmann1, Maike Büttner-Herold2, Markus Hecht1, Rainer Fietkau1 and Luitpold Distel1*
Abstract Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for nonprofessional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can nonprofessionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival. Keywords: Cell-in-cell, Non-professional phagocytosis, Senescence, Cannibalism, Entosis, Rectal cancer, Camptothecin, Prognostic factor and survival
Background Radiation therapy of cancer achieves its therapeutic effect through the induction of different types of cell death. The predominant types of cell death are apoptosis and necrosis, which are also the most widely discussed types of cell death recognized in current morphological nomenclature [1]. * Correspondence: [email protected] † Dorian Gottwald and Florian Putz contributed equally to this work. 1 Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany Full list of author information is available at the end of the article
Apoptotic and necrotic cell death as well as most other kinds of cell death mostly lead to a rapid elimination of cell remnants. In striking contrast, however, it is well known from radiotherapy that most malignancies do not resolve during multi-week fractionated radiation treatment. Indeed, most malignancies require several weeks after the end of treatment to show volumetric tumor regression in clinical and imaging assessment [2, 3]. In rectal cancer for example,
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