title: Interference of Ca²⁺ with the proliferation of SCCOHT-1 and ovarian adenocarcinoma cells.
abstract: A recently established cellular model for the rare small cell carcinoma of the ovary hypercalcemic type (SCCOHT-1) was characterized in comparison to ovarian adenocarcinoma cells (NIH:OVCAR-3 and SK-OV-3). The different cancer populations exhibited a common sensitivity in acidic pH milieu and a continuous proliferation in alkaline medium of pH 8.0-9.0. In the presence of elevated Ca2+ concentrations, the ovarian cancer cells demonstrated a progressively reduced proliferation within 72 h in contrast to other tumor types such as breast cancer cells. This significant growth inhibition was calcium-specific since the proliferation was unaffected after culture of the ovarian cancer cells in the presence of similar concentrations of other cations. The Ca2+ effects on the ovarian cancer cells were associated with marked differences in the activation of intracellular signaling pathways including enhanced phosphorylation of the p42/44 MAP kinase (Thr202/Tyr204). Further analysis of the signaling pathway revealed a significantly enhanced Ca2+-dependent and p42/44 MAP kinase activation-mediated prostaglandin E2 (PGE2) production in SK-OV-3 and SCCOHT-1 and to a lesser extent in NIH:OVCAR-3 cells. Vice versa, exogenous PGE2 did not affect the proliferative capacity of the ovarian cancer cells and inhibition of the Ca2+-mediated MAP kinase activation did not abolish the Ca2+-mediated cytotoxicity. Collectively, these data suggest that multiple pathways are activated by exogenous Ca2+ in the different ovarian cancer cells, including a specific MAP kinase signaling cascade with subsequent PGE2 production and a parallel pathway for the induction of cell death.
authors: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors: Anna
authors: A
authors: Otte
authors: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors: Finn
authors: F
authors: Rauprich
authors: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors: Juliane
authors: J
authors: von der Ohe
authors: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors: Peter
authors: P
authors: Hillemanns
authors: Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany.
authors: Ralf
authors: R
authors: Hass
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000150:complications*; D020935:MAP Kinase Signaling System; D010051:Ovarian Neoplasms / Q000473:pathology*
chemical_list: D015232:Dinoprostone; D002118:Calcium