Culture of ascitic ovarian cancer cells as a clinically-relevant ex vivo model for the assessment of biological therapies.
There are few in vitro models of human ovarian cancer suitable for the assessment of biological therapies. We have established short-term cultures of ovarian carcinoma cells from ascites, maintained in suspension in ascitic fluid to help preserve the original tumor cell microenvironment. We assessed the effects of a potential biological therapeutic agent, interferon-alpha (IFN alpha), on ovarian cell phenotype. In total, eight cultures were established from seven patients. Quantitative changes in cell surface phenotype were determined by flow cytometry for HLA-ABC, HLA-DR, TAG72, CA125, HMFG1 and HMFG2 antigens. The amount of CA125 antigen shed into the culture media was also assessed. Variations in cell surface phenotype between specimens probably reflected the specific cytokine milieu of the ascites as well as idiotypic differences between tumors. Nevertheless, there were consistent phenotypic responses to IFN alpha, with up-regulation of MHC Class I but down-regulation of the HMFG1 and HMFG2 antigens from the cell surface. The results suggest that this approach may be useful in patient selection and for optimizing biological therapies, as it enables patients' individual tumor responses to exogenous cytokine to be studied against the background of the endogenous cytokine milieu.
Metcalf
K S
KS
ICRF Cancer Medicine Research Unit, St. James's University Hospital, Leeds, United Kingdom.
Selby
P J
PJ
Trejdosiewicz
L K
LK
Southgate
J
J
D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D018394:CA-125 Antigen / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000032:analysis*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000473:pathology
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D006680:HLA Antigens