Müllerian inhibiting substance/anti-Müllerian hormone: A novel treatment for gynecologic tumors
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Müllerian inhibiting substance (MIS), also called anti-Müllerian hormone (AMH), is a member of the transforminggrowth factor-β super-family of growth and differentiation response modifiers. It is produced in immature Sertolicells in male embryos and binds to MIS/AMH receptors in primordial Müllerian ducts to cause regression of femalereproductive structures that are the precursors to the fallopian tubes, the surface epithelium of the ovaries, theuterus, the cervix, and the upper third of the vagina. Because most gynecologic tumors originate from Müllerian ductderivedtissues, and since MIS/AMH causes regression of the Müllerian duct in male embryos, it is expected to inhibitthe growth of gynecologic tumors. Purified recombinant human MIS/AMH causes growth inhibition of epithelialovarian cancer cells and cell lines in vitro and in vitro via MIS receptor-mediated mechanism. Furthermore, several linesof evidence suggest that MIS/AMH inhibits proliferation in tissues and cell lines of other MIS/AMH receptor-expressinggynecologic tumors such as cervical, endometrial, breast, and in endometriosis as well. These findings indicatethat bioactive MIS/AMH recombinant protein should be tested in patients against tumors expressing the MIS/AMHreceptor complex, perhaps beginning with ovarian cancer because it has the worst prognosis. The molecular toolsto identify MIS/AMH receptor expressing ovarian and other cancers are in place, thus, it is possible to select patientsfor treatment. An MIS/AMH ELISA exists to follow administered doses of MIS/AMH, as well. Clinical trials await theproduction of sufficient supplies of qualified recombinant human MIS/AMH for this purpose
Abstract
Müllerian inhibiting substance (MIS), also called anti-Müllerian hormone (AMH), is a member of the transforminggrowth factor-β super-family of growth and differentiation response modifiers. It is produced in immature Sertolicells in male embryos and binds to MIS/AMH receptors in primordial Müllerian ducts to cause regression of femalereproductive structures that are the precursors to the fallopian tubes, the surface epithelium of the ovaries, theuterus, the cervix, and the upper third of the vagina. Because most gynecologic tumors originate from Müllerian ductderivedtissues, and since MIS/AMH causes regression of the Müllerian duct in male embryos, it is expected to inhibitthe growth of gynecologic tumors. Purified recombinant human MIS/AMH causes growth inhibition of epithelialovarian cancer cells and cell lines in vitro and in vitro via MIS receptor-mediated mechanism. Furthermore, several linesof evidence suggest that MIS/AMH inhibits proliferation in tissues and cell lines of other MIS/AMH receptor-expressinggynecologic tumors such as cervical, endometrial, breast, and in endometriosis as well. These findings indicatethat bioactive MIS/AMH recombinant protein should be tested in patients against tumors expressing the MIS/AMHreceptor complex, perhaps beginning with ovarian cancer because it has the worst prognosis. The molecular toolsto identify MIS/AMH receptor expressing ovarian and other cancers are in place, thus, it is possible to select patientsfor treatment. An MIS/AMH ELISA exists to follow administered doses of MIS/AMH, as well. Clinical trials await theproduction of sufficient supplies of qualified recombinant human MIS/AMH for this purpose
참고문헌 (119)
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