(NIH:OVCAR-3) with Androgen and Estrogen Receptors Characterization of a Human Ovarian Carcinoma Cell Line

A cell line, NIH:OVCAR-3, has been established from the malignant ascites of a patient with progressive adenocarcinoma of the ovary after combination chemotherapy with cyclophosphamide, Adriamycin, and cisplatin. OVCAR-3 grows as a cobble stone-like monolayer with foci of multilayering, is tumorigenic in athymic mice, clones in agarose, and has an abnormal karyotype which includes a homogeneous staining region and a double minute chromosome. The cultured cells and xenografts contain cytoplasmic androgenand estrogen-binding macromolecules with the specificity of the respective steroid hormone receptors. These components have sedimentation coefficients of 7 to 9S in low-salt sucrose-density gradients, have dissociation constants of 250 and 9.6 pM, and are present at concentrations of 30 and 28 fmol/mg cytosol protein characteristic of androgen and estro gen receptors, respectively. OVCAR-3 is resistant in vitro to clinically relevant concentrations of Adriamycin (5 x 10~8 M), melphalan (5 x 10~6 M), and cisplatin (5 x 10~7 M) with survival compared to untreated controls of 43,45, and 77%, respectively. Furthermore, there are multiple histological similarities between the patient's original tumor, the cell line, and the transplantable tumor. These data indicate that OVCAR-3 may be of use for investi gations as to the significance of androgens and estrogens and the mechanisms of cytotoxic drug resistance in ovarian cancer.