Human ovarian cancer xenografts in nude mice: characterization and analysis of antigen expression.
We have characterized 13 different human ovarian cancer xenografts grown subcutaneously in nude mice. The tumor lines represented 5 histological subtypes: serous (4), mucinous (4), clear-cell carcinoma (1), carcinosarcoma (1) and undifferentiated (3). The specific histology and the degree of differentiation resembled those of the original patients' tumors and were maintained upon serial transfer. Volume doubling times of the xenografts ranged from 3.5 to 15 days. The xenografts were also analyzed for their antigen expression using 20 monoclonal antibodies (MAbs) reactive with 15 tumor-associated antigens. Immunohistochemical examination of tissue sections showed a positive reaction pattern with MAbs 115D8, 140C1, 139H2, 175C5, HMFG1 and HMFG2, each recognizing episialin, as well as with MAbs AUA1, 358.4.32 and 199-157 in xenografts of the serous, mucinous and clear-cell carcinoma subtype. MAb OC125 was reactive with xenografts of the serous subtypes. Other antibodies, such as 494 and OV-TL3 infrequently demonstrated positive reactions. Reactivity of all MAbs was low in the carcinosarcoma and undifferentiated tumor lines. With the exception of AUA1, 495 and 126E5, all MAbs revealed a heterogeneous staining pattern. MAbs against episialin and OC125 predominantly stained the apical site of the tumor cells. Strongest reactivity with almost all histological subtypes was observed with MAbs 115D8, 140C1, 139H2 and AUA1. In cases where we were able to compare the patients' tumor tissue with the respective xenografts, retention of antigen expression was demonstrated in each instance. Release of tumor-associated antigens was shown for CA125 in 2 serous-tumor lines, for CA15.3 in 1 serous-tumor line, and for CEA in 3 lines of the mucinous subtype. This panel of human tumor xenografts could be a valuable tool to determine the potential usefulness of MAb-guided therapy in ovarian cancer.
Molthoff
C F
CF
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Calame
J J
JJ
Pinedo
H M
HM
Boven
E
E
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002277:Carcinoma / Q000276:immunology; D002296:Carcinosarcoma / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D014183:Transplantation, Heterologous
D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D002272:Carcinoembryonic Antigen; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase