Highly purified müllerian inhibiting substance inhibits human ovarian cancer in vivo.
OBJECTIVE
Müllerian inhibiting substance (MIS) causes Müllerianduct regression in mammalian, avian, and reptilian embryos; MIS also inhibits growth in vitro of Müllerian-derived cell lines and primary cells from human ovarian carcinomas. We hypothesize that highly purified MIS delivered parenterally inhibits ovarian cancer in vivo.


METHODS
To test the efficacy of highly purified MIS against ovarian cancer cell lines in vivo, we treated immunosuppressed mice with MIS after implanting OVCAR 8 or IGROV 1 human ovarian cancer cells beneath the renal capsules and measured tumor volume over time. Animals were treated with daily injections of 10 micro g of purified exogenous recombinant human MIS or by endogenous MIS secreted from cells growing on biodegradable mesh.


RESULTS
The average graft size ratio (change in size compared with starting size) of the OVCAR 8 tumor implants was larger in the control animals than in animals treated for 2 weeks (P < 0.019) or 3 weeks (P < 0.001) with parenteral MIS, or after treating with MIS produced from transfected cells, which impregnated the biodegradable mesh (P = 0.02). The average graft size ratio of the IGROV 1 tumors was also larger in the control animals than in those treated with injected MIS (P = 0.0174).


CONCLUSIONS
Highly purified recombinant human MIS, delivered parenterally, or MIS produced endogenously causes inhibition of human ovarian cancer cell lines in vivo, providing convincing preclinical evidence to support the use of MIS as a parenteral agent for the treatment of ovarian cancer.
Stephen
Antonia E
AE
Pediatric Surgical Research Laboratories, Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Pearsall
Lisa A
LA
Christian
Benjamin P
BP
Donahoe
Patricia K
PK
Vacanti
Joseph P
JP
MacLaughlin
David T
DT
D000818:Animals; D054304:Anti-Mullerian Hormone; D016466:CHO Cells; D006224:Cricetinae; D005260:Female; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009095:Mullerian Ducts / Q000276:immunology; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013735:Testicular Hormones / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D006131:Growth Inhibitors; D011994:Recombinant Proteins; D013735:Testicular Hormones; D054304:Anti-Mullerian Hormone