title: Phagocytosis of dying tumor cells by human peritoneal mesothelial cells.
abstract: 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 'amateur' 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.
authors.affiliation: Department of Immunology, University of Tübingen, Tübingen 72076, Germany.
authors.forename: Britta Janina
authors.initials: BJ
authors.lastname: Wagner
authors.forename: Dennis
authors.initials: D
authors.lastname: Lindau
authors.forename: Dagmar
authors.initials: D
authors.lastname: Ripper
authors.forename: York-Dieter
authors.initials: YD
authors.lastname: Stierhof
authors.forename: Jörg
authors.initials: J
authors.lastname: Glatzle
authors.forename: Maria
authors.initials: M
authors.lastname: Witte
authors.forename: Henning
authors.initials: H
authors.lastname: Beck
authors.forename: Hildegard
authors.initials: H
authors.lastname: Keppeler
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
mesh_terms: D017209:Apoptosis / Q000502:physiology; D018938:Caco-2 Cells; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D018613:Microscopy, Confocal; D010051:Ovarian Neoplasms / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000473:pathology* / Q000556:secondary; D010537:Peritoneum / Q000473:pathology*; D010587:Phagocytosis / Q000502:physiology*; D059016:Tumor Microenvironment