Inhibition of ovarian cancer cell proliferation in vivo and incorporation of 3H-thymidine in vitro after follicle regulatory protein administration.
Follicle regulatory protein immunoreactivity and biologic activity were measured in ascites from a patient with juvenile granulosa cell tumor. Microscopic examination of immunohistochemical staining of a juvenile granulosa cell tumor with anti-follicle regulatory protein antisera showed homogeneous cytosolic expression of follicle regulatory protein throughout the tumor. Tumor cells were injected subcutaneously into nude mice. Partially purified follicle regulatory protein (50 micrograms/day) was then injected daily for 10 days, or for 25 days once the tumor became palpable. Treatment with follicle regulatory protein significantly slowed the rate of tumor growth with both treatments. To test the tissue specificity of the effect, a metastatic, well-differentiated endometrial adenocarcinoma was also grown in nude mice. Follicle regulatory protein treatment did not alter the rate of tumor growth. An in vitro clonigenic assay confirmed these in vivo results. Partially purified follicle regulatory protein had a biphasic effect on the proliferation of juvenile granulosa tumor cell but did not affect the proliferation of endometrial adenocarcinoma cells. Clonigenic assays were performed on five ovarian adenocarcinomas passaged in vitro, and these tumor cells exhibited a biphasic response to follicle regulatory protein. Immunoneutralization studies showed that this biphasic response was due to impurities in the follicle regulatory protein preparations. The longer the exposure of the tumor cells to follicle regulatory protein, the greater the degree of inhibition of proliferation. In summary, administration of follicle regulatory protein slowed tumor growth through a direct effect on the tumor cell rather than an indirect effect on the hormonal or immune status of the host.
Rodgers
K E
KE
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles.
Montz
F J
FJ
Scott
L
L
Condon
S
S
Fujimori
K
K
diZerega
G S
GS
D000230:Adenocarcinoma / Q000473:pathology; D000328:Adult; D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006106:Granulosa Cell Tumor / Q000473:pathology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009865:Oocytes / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014410:Tumor Stem Cell Assay
D006131:Growth Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C018355:intraovarian peptides; D014316:Tritium; D013936:Thymidine