title: An immunocompetent, orthotopic mouse model of epithelial ovarian cancer utilizing tissue engineered tumor cell sheets.
abstract: Despite the development of a myriad of anticancer drugs that appeared promising in preclinical ovarian cancer animal models, they failed to predict efficacy in clinical testing. To improve the accuracy of preclinical testing of efficacy and toxicity, including pharmacokinetic and pharmacodynamic evaluations, a novel animal model was developed and characterized. In this study, murine ID8 (epithelial ovarian cancer [EOC]) cells as injected cell suspensions (ICS) and as intact cultured monolayer cell sheets (CS) were injected or surgically grafted, respectively, into the left ovarian bursa of 6-8 week-old, female C57BL/6 black mice and evaluated at 8 and 12 weeks after engraftment. Tumor volumes at 8 weeks were as follows: 30.712 ± 18.800 mm(3) versus 55.837 ± 10.711 mm(3) for ICS and CS, respectively, p = 0.0990 (n = 5). At 12 weeks, tumor volumes were 128.129 ± 44.018 mm(3) versus 283.953 ± 71.676 mm(3) for ICS and CS, respectively, p = 0.0112 (n = 5). The ovarian weights at 8 and 12 weeks were 0.02138 ± 0.01038 g versus 0.04954 ± 0.00667 g for ICS and CS, respectively (8 weeks), p = 0.00602 (n = 5); and 0.10594 ± 0.03043 g versus 0.39264 ± 0.09271 g for ICS and CS, respectively (12 weeks), p = 0.0008 (n = 5). These results confirm a significant accelerated tumorigenesis in CS-derived tumors compared with ICS-derived tumors when measured by tumor volume/time and ovarian weight/time. Furthermore, the CS-derived tumors closely replicated the metastatic spread found in human EOC and histopathological identity with the primary tumor of origin.
authors.affiliation: 1 Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Tokyo, Japan .
authors.forename: Ayumi
authors.initials: A
authors.lastname: Arauchi
authors.forename: Chieh-Hsiang
authors.initials: CH
authors.lastname: Yang
authors.forename: Sungpil
authors.initials: S
authors.lastname: Cho
authors.forename: Elke A
authors.initials: EA
authors.lastname: Jarboe
authors.forename: C Matthew
authors.initials: CM
authors.lastname: Peterson
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Margit M
authors.initials: MM
authors.lastname: Janát-Amsbury
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D048430:Cell Shape; D004195:Disease Models, Animal; D010450:Endopeptidases; D015622:Epithelioid Cells / Q000473:pathology; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007121:Immunocompetence; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012697:Serine Endopeptidases; D042461:Vascular Endothelial Growth Factor A; D000099167:Fibroblast Activation Protein Alpha
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