title: A tumor-derived population (SCCOHT-1) as cellular model for a small             cell ovarian carcinoma of the hypercalcemic type.
abstract: The small cell ovarian carcinoma of the hypercalcemic type (SCCOHT) represents             an aggressive tumor with poor prognosis predominantly affecting young women and             so far, no cell line or animal model is available to investigate this devastating             disease. Biopsy material from a recurrent SCCOHT was subjected to an explant culture             to obtain an adherent and continuously proliferating cell population. Morphological             and functional characterization revealed a heterogeneous population (SCCOHT-1)             of about 13 µm in diameter and approximately 36 h of doubling time. Flow cytometric             analysis of surface markers demonstrated the expression of CD15, CD29, CD44 and             CD90 paralleled by the presence of cytokeratins and vimentin. Cytogenetic analysis             and high-resolution oligo-array comparative genomic hybridization (aCGH) demonstrated             a stable karyotype including deletions of the PARK2, CSMD1, GRIN2B and ATF7IP             genes. Following lentiviral transduction with a GFP vector, the labeled SCCOHT-derived             cells were subjected to CCE to separate distinct subpopulations as evidenced by             cell cycle analysis. Subcutaneous injection of these subpopulations into NOD/SCID             mice exhibited hypercalcemia and a tumor development in 100% of the mice. Re-cultivation             of the mouse tumors revealed an outgrowth of SCCOHT-derived phenotypes and all             cell populations expressed high telomerase activity. Moreover, histopathological             evaluation demonstrated close similarities between the mouse tumors and the original             patient tumor. In conclusion, SCCOHT-1 cells provide a study platform to investigate             this rare disease and to examine effective and sufficient therapeutic strategies             for this rather unknown type of cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Medical University,                     Hannover, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Otte
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Doris
authors.initials: D
authors.lastname: Steinemann
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Stephanie
authors.initials: S
authors.lastname: Groos
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Kreipe
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.forename: Thomas
authors.initials: T
authors.lastname: Neumann
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.forename: Tjoung-Won
authors.initials: TW
authors.lastname: Park-Simon
authors.forename: Ralf
authors.initials: R
authors.lastname: Hass
mesh_terms: D059786:Abnormal Karyotype; D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002118:Calcium / Q000097:blood; D018288:Carcinoma, Small Cell / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure*; D049109:Cell Proliferation; D048430:Cell Shape; D005260:Female; D042822:Genomic Instability; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D019098:Telomerase / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D019098:Telomerase; D002118:Calcium