{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:16:01Z","timestamp":1791166561472,"version":"4.1.0"},"reference-count":43,"publisher":"The Company of Biologists","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,15]]},"abstract":"<jats:p>Peritoneal carcinomatosis is an advanced form of metastatic disease characterized by cancer cell dissemination onto the peritoneum. It is commonly observed in ovarian and colorectal cancers and is associated with poor patient survival. Novel therapies consist of cytoreductive surgery in combination with intraperitoneal chemotherapy, aiming at tumor cell death induction. The resulting dying tumor cells are considered to be eliminated by professional as well as semi-professional phagocytes. In the present study, we have identified a hitherto unknown type of \u2018amateur\u2019 phagocyte in this environment: human peritoneal mesothelial cells (HMCs). We demonstrate that HMCs engulf corpses of dying ovarian and colorectal cancer cells, as well as other types of apoptotic cells. Flow cytometric, confocal and electron microscopical analyses revealed that HMCs ingest dying cell fragments in a dose- and time-dependent manner and the internalized material subsequently traffics into late phagolysosomes. Regarding the mechanisms of prey cell recognition, our results show that HMCs engulf apoptotic corpses in a serum-dependent and -independent fashion and quantitative real-time PCR (qRT-PCR) analyses revealed that diverse opsonin receptor systems orchestrating dying cell clearance are expressed in HMCs at high levels. Our data strongly suggest that HMCs contribute to dying cell removal in the peritoneum, and future studies will elucidate in what manner this influences tumor cell dissemination and the antitumor immune response.<\/jats:p>","DOI":"10.1242\/jcs.078907","type":"journal-article","created":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T00:27:23Z","timestamp":1303950443000},"page":"1644-1654","source":"Crossref","is-referenced-by-count":28,"title":["Phagocytosis of dying tumor cells by human peritoneal mesothelial cells"],"prefix":"10.1242","volume":"124","author":[{"given":"Britta Janina","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Immunology, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"},{"name":"Department of General, Visceral, and Transplantation Surgery, University Hospital T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Lindau","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Ripper","sequence":"additional","affiliation":[{"name":"Center of Plant Molecular Biology, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"York-Dieter","family":"Stierhof","sequence":"additional","affiliation":[{"name":"Center of Plant Molecular Biology, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Glatzle","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery, University Hospital T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Witte","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery, University Hospital T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Beck","sequence":"additional","affiliation":[{"name":"Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"},{"name":"Graduate School for Cellular and Molecular Neurosciences, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildegard","family":"Keppeler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Lauber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"},{"name":"Department of Radiation Oncology, LMU Munich, Munich 81377, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Georg","family":"Rammensee","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"K\u00f6nigsrainer","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, and Transplantation Surgery, University Hospital T\u00fcbingen, T\u00fcbingen 72076, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042521305287400_R1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0092-8674(02)00819-X","article-title":"How to eat something bigger than your head","volume":"110","author":"Aderem","year":"2002","journal-title":"Cell"},{"key":"2021042521305287400_R2","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1007\/s00436-009-1565-z","article-title":"Mechanism involved in phagocytosis and killing of Listeria monocytogenes by Acanthamoeba polyphaga","volume":"105","author":"Akya","year":"2009","journal-title":"Parasitol. Res."},{"key":"2021042521305287400_R3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10585-005-2893-8","article-title":"ICAM-1 mediated peritoneal carcinomatosis, a target for therapeutic intervention","volume":"22","author":"Alkhamesi","year":"2005","journal-title":"Clin. Exp. Metastasis"},{"key":"2021042521305287400_R4","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1242\/jcs.110.6.731","article-title":"Internalized Listeria monocytogenes modulates intracellular trafficking and delays maturation of the phagosome","volume":"110","author":"Alvarez-Dominguez","year":"1997","journal-title":"J. Cell Sci."},{"key":"2021042521305287400_R5","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1006\/smim.2001.0332","article-title":"Membrane dynamics in phagocytosis","volume":"13","author":"Booth","year":"2001","journal-title":"Semin. Immunol."},{"key":"2021042521305287400_R6","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/S0344-0338(89)80027-5","article-title":"What's new in intraperitoneal test on Kevlar (asbestos substitute)?","volume":"185","author":"Brinkmann","year":"1989","journal-title":"Pathol. Res. Pract."},{"key":"2021042521305287400_R7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1476-4598-9-47","article-title":"Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells","volume":"9","author":"Bryant","year":"2010","journal-title":"Mol. Cancer"},{"key":"2021042521305287400_R8","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1677\/jme.0.0320497","article-title":"Phosphatidylserine receptor cooperates with high-density lipoprotein receptor in recognition of apoptotic cells by thymic nurse cells","volume":"32","author":"Cao","year":"2004","journal-title":"J. Mol. Endocrinol."},{"key":"2021042521305287400_R9","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.124.5.677","article-title":"Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus","volume":"124","author":"Desjardins","year":"1994","journal-title":"J. Cell Biol."},{"key":"2021042521305287400_R10","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1242\/jcs.108.3.967","article-title":"Phagocytosis of apoptotic bodies by liver endothelial cells","volume":"108","author":"Dini","year":"1995","journal-title":"J. Cell Sci."},{"key":"2021042521305287400_R11","doi-asserted-by":"crossref","first-page":"4717","DOI":"10.4049\/jimmunol.172.8.4717","article-title":"Macrophages and stromal cells phagocytose apoptotic bone marrow-derived B lineage cells","volume":"172","author":"Dogusan","year":"2004","journal-title":"J. Immunol."},{"key":"2021042521305287400_R12","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3109\/15476910903204058","article-title":"AnnexinA5 renders dead tumor cells immunogenic-implications for multimodal cancer therapies","volume":"6","author":"Frey","year":"2009","journal-title":"J. Immunotoxicol."},{"key":"2021042521305287400_R13","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/sj.cdd.4402148","article-title":"Cell death modalities: classification and pathophysiological implications","volume":"14","author":"Galluzzi","year":"2007","journal-title":"Cell Death Differ."},{"key":"2021042521305287400_R14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2567.2004.01959.x","article-title":"The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically?","volume":"113","author":"Gregory","year":"2004","journal-title":"Immunology"},{"key":"2021042521305287400_R15","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/sj.ki.5001710","article-title":"Staphylococcus aureus induces caspase-independent cell death in human peritoneal mesothelial cells","volume":"70","author":"Haslinger-L\u00f6ffler","year":"2006","journal-title":"Kidney Int."},{"key":"2021042521305287400_R16","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.4049\/jimmunol.158.9.4389","article-title":"Human glomerular mesangial cell phagocytosis of apoptotic neutrophils: mediation by a novel CD36-independent vitronectin receptor\/thrombospondin recognition mechanism that is uncoupled from chemokine secretion","volume":"158","author":"Hughes","year":"1997","journal-title":"J. Immunol."},{"key":"2021042521305287400_R17","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1242\/jcs.03463","article-title":"Journey to the grave: signalling events regulating removal of apoptotic cells","volume":"120","author":"Kinchen","year":"2007","journal-title":"J. Cell Sci."},{"key":"2021042521305287400_R18","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/ncb1718","article-title":"A pathway for phagosome maturation during engulfment of apoptotic cells","volume":"10","author":"Kinchen","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"2021042521305287400_R19","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1016\/j.cub.2006.09.043","article-title":"Apoptotic cells induce a phosphatidylserine-dependent homeostatic response from phagocytes","volume":"16","author":"Kiss","year":"2006","journal-title":"Curr. Biol."},{"key":"2021042521305287400_R20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1097-2765(04)00237-0","article-title":"Clearance of apoptotic cells: getting rid of the corpses","volume":"14","author":"Lauber","year":"2004","journal-title":"Mol. Cell"},{"key":"2021042521305287400_R21","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.jamcollsurg.2006.12.048","article-title":"Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures","volume":"204","author":"Levine","year":"2007","journal-title":"J. Am. Coll. Surg."},{"key":"2021042521305287400_R22","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1242\/jcs.114.6.1061","article-title":"Phagocytosis and the actin cytoskeleton","volume":"114","author":"May","year":"2001","journal-title":"J. Cell Sci."},{"key":"2021042521305287400_R23","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1084\/jem.188.12.2313","article-title":"Complement-dependent clearance of apoptotic cells by human macrophages","volume":"188","author":"Mevorach","year":"1998","journal-title":"J Exp. Med."},{"key":"2021042521305287400_R24","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1083\/jcb.146.4.703","article-title":"Extranuclear apoptosis. The role of the cytoplasm in the execution phase","volume":"146","author":"Mills","year":"1999","journal-title":"J. Cell Biol."},{"key":"2021042521305287400_R25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/sj.cdd.4401517","article-title":"Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release","volume":"12","author":"Monks","year":"2005","journal-title":"Cell Death Differ."},{"key":"2021042521305287400_R26","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1046\/j.1440-1843.2002.00404.x","article-title":"Mesothelial cells: their structure, function and role in serosal repair","volume":"7","author":"Mutsaers","year":"2002","journal-title":"Respirology"},{"key":"2021042521305287400_R27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S1357-2725(03)00242-5","article-title":"The mesothelial cell","volume":"36","author":"Mutsaers","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2021042521305287400_R28","first-page":"1","article-title":"Structure and function of mesothelial cells","volume":"134","author":"Mutsaers","year":"2007","journal-title":"Cancer Treat. Res."},{"key":"2021042521305287400_R29","doi-asserted-by":"crossref","first-page":"9535","DOI":"10.1073\/pnas.95.16.9535","article-title":"Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged\/apoptotic cells in endothelial cells","volume":"95","author":"Oka","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042521305287400_R30","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1242\/jcs.049569","article-title":"Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages","volume":"122","author":"Park","year":"2009","journal-title":"J. Cell Sci."},{"key":"2021042521305287400_R31","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0960-9822(00)00598-4","article-title":"Differences between the clearance of apoptotic cells by professional and non-professional phagocytes","volume":"10","author":"Parnaik","year":"2000","journal-title":"Curr. Biol."},{"key":"2021042521305287400_R32","doi-asserted-by":"crossref","first-page":"5296","DOI":"10.1074\/jbc.M706586200","article-title":"Migration to apoptotic \u201cfind-me\u201d signals is mediated via the phagocyte receptor G2A","volume":"283","author":"Peter","year":"2008","journal-title":"J. Biol. Chem."},{"key":"2021042521305287400_R33","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1067\/mai.2001.119414","article-title":"Human alveolar epithelial cells engulf apoptotic eosinophils by means of integrin- and phosphatidylserine receptor-dependent mechanisms: a process upregulated by dexamethasone","volume":"108","author":"Sexton","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"2021042521305287400_R34","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1158\/0008-5472.CAN-08-2678","article-title":"Vascular cell adhesion molecule-1 is a regulator of ovarian cancer peritoneal metastasis","volume":"69","author":"Slack-Davis","year":"2009","journal-title":"Cancer Res."},{"key":"2021042521305287400_R35","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/ki.1990.150","article-title":"Isolation, culture and characterization of human peritoneal mesothelial cells","volume":"37","author":"Stylianou","year":"1990","journal-title":"Kidney Int."},{"key":"2021042521305287400_R36","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1007\/s10495-010-0516-6","article-title":"Mechanisms of failed apoptotic cell clearance by phagocyte subsets in cardiovascular disease","volume":"15","author":"Thorp","year":"2010","journal-title":"Apoptosis"},{"key":"2021042521305287400_R37","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/(SICI)1521-1878(200003)22:3<255::AID-BIES7>3.0.CO;2-R","article-title":"Phagosome dynamics and function","volume":"22","author":"Tjelle","year":"2000","journal-title":"BioEssays"},{"key":"2021042521305287400_R38","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/sj.cdd.4402286","article-title":"DNA damage induces two distinct modes of cell death in ovarian carcinomas","volume":"15","author":"Vakifahmetoglu","year":"2008","journal-title":"Cell Death Differ."},{"key":"2021042521305287400_R39","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1007\/s10620-007-9778-4","article-title":"Inflammatory cytokines stimulate the adhesion of colon carcinoma cells to mesothelial monolayers","volume":"52","author":"van Grevenstein","year":"2007","journal-title":"Dig. Dis. Sci."},{"key":"2021042521305287400_R40","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1182\/blood.V94.8.2827.420a04_2827_2835","article-title":"Resting and cytokine-stimulated human small airway epithelial cells recognize and engulf apoptotic eosinophils","volume":"94","author":"Walsh","year":"1999","journal-title":"Blood"},{"key":"2021042521305287400_R41","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1242\/dev.127.24.5245","article-title":"Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos","volume":"127","author":"Wood","year":"2000","journal-title":"Development"},{"key":"2021042521305287400_R42","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/ni1146","article-title":"Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA","volume":"6","author":"Yoshida","year":"2005","journal-title":"Nat. Immunol."},{"key":"2021042521305287400_R43","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.tcb.2008.08.002","article-title":"Phagosome maturation during the removal of apoptotic cells: receptors lead the way","volume":"18","author":"Zhou","year":"2008","journal-title":"Trends Cell Biol."}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/124\/10\/1644\/1447482\/1644.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/124\/10\/1644\/1447482\/1644.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T14:09:18Z","timestamp":1686060558000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/124\/10\/1644\/31723\/Phagocytosis-of-dying-tumor-cells-by-human"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,15]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2011,5,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.078907","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2011,5,15]]}}}