David T. MacLaughlin, PhD
Associate Professor, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School
Associate Director, Pediatric Surgical Research Laboratories, Massachusetts General Hospital
DF/HCC Program AffiliationGynecologic Cancers
A major focus of our group is to test the hypothesis that Müllerian Inhibiting Substance, a gonadal protein that causes the regression of Müllerian structures in fetal males, can be used to treat malignancies of Müllerian origin in adult females including the highly lethal serous cystadenomas of the ovary. We predict that this naturally occurring biological response modifier will be non-toxic and highly specific since it should inhibit the growth only of cells expressing the functional MIS receptor complex. In support of our hypothesis our laboratory recently reported that five of six human ovarian cancer cell lines expressed the MIS type II receptor, specifically bound recombinant human Müllerian Inhibiting Substance, rhMIS, and were growth inhibited by the recombinant protein in vitro. Perhaps of greater significance, however, is our newest finding that 56% of the ovarian cancer cell samples harvested from the abdominal ascites of 27 patients bound rhMIS and nearly all of these MIS binders also expressed the type II receptor and were growth inhibited in vitro. These results further validate our hypothesis and suggest that by screening ascites cells for MIS receptor expression, rhMIS binding and responsiveness in vitro, it may be possible to distinguish potential responders from non-responders in subsequent clinical trials using recombinant human MIS.
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