title: Interleukin-6 receptor enhances early colonization of the murine omentum by upregulation of a mannose family receptor, LY75, in ovarian tumor cells.
abstract: One of the earliest metastatic events in human ovarian cancer, tumor spread to the omentum, may be influenced by expression of interleukin 6 (IL6) and its cognate receptor (IL6Rα). Previous reports have shown that IL6 and IL6Rα expression is elevated in the serum and ascites of patients with ovarian cancer and that this can influence in vitro processes such as cell survival, proliferation and migration. In this study, overexpression of IL6Rα, and to a lesser extent IL6, enhanced tumor growth on the omentum. Moreover, adherence to plastic and to peritoneal extracellular matrix components was enhanced in tumor cells overexpressing IL6 or IL6Rα. Host production of IL6 and IL6Rα was also sufficient to influence tumor adherence to the omentum. Expression of LY75/CD205/DEC205, a collagen-binding mannose family receptor, was directly influenced by IL6Rα expression. Blocking LY75 with antibody reduced the adherence of tumor cells overexpressing IL6Rα to matrices in vitro and to the omentum. The association between IL6Rα expression and LY75 expression has not been previously reported, and the promotion of cellular adherence is a novel role for LY75. These studies indicate that overexpression of LY75 may be an additional mechanism by which IL6 signaling influences the progression of ovarian cancer, and suggests that blocking LY75 could be a valuable clinical strategy for reducing the early metastasis of ovarian cancer.
authors: Department of Cancer and Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA.
authors: Premkumar Vummidi
authors: PV
authors: Giridhar
authors: Holly M
authors: HM
authors: Funk
authors: Catherine A
authors: CA
authors: Gallo
authors: Aleksey
authors: A
authors: Porollo
authors: Carol A
authors: CA
authors: Mercer
authors: David R
authors: DR
authors: Plas
authors: Angela F
authors: AF
authors: Drew
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D005109:Extracellular Matrix; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000502:physiology; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D009361:Neoplasm Invasiveness; D009852:Omentum / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C093569:DEC-205 receptor; D015850:Interleukin-6; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D019947:Receptors, Interleukin-6; D008358:Mannose