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A panel of eight was initially selected from 95 human cell surface antigens as each was shared among human ovarian primary cancers, ovarian cancer cell lines, and normal fimbria. A total of 150 combinations of markers were reduced to a panel of three\u2014CD44, CD24, and Epcam\u2014which selected, in three ovarian cancer cell lines, those cells which best formed colonies. Cells expressing CD44, CD24, and Epcam exhibited stem cell characteristics of shorter tumor-free intervals in vivo after limiting dilution, and enhanced migration in invasion assays in vitro. Also, doxorubicin, cisplatin, and paclitaxel increased this enriched population which, conversely, was significantly inhibited by M\u00fcllerian inhibiting substance (MIS) or the MIS mimetic SP600125. These findings demonstrate that flow cytometry can be used to detect a population which shows differential drug sensitivity, and imply that treatment of patients can be individualized to target both stem\/progenitor cell enriched and nonenriched subpopulations. The findings also suggest that this population, amenable to isolation by flow cytometry, can be used to screen for novel treatment paradigms, including biologic agents such as MIS, which will improve outcomes for patients with ovarian cancer.<\/jats:p>","DOI":"10.1073\/pnas.1012667107","type":"journal-article","created":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T23:11:57Z","timestamp":1287184317000},"page":"18874-18879","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":85,"title":["M\u00fcllerian inhibiting substance preferentially inhibits stem\/progenitors in human ovarian cancer cell lines compared with chemotherapeutics"],"prefix":"10.1073","volume":"107","author":[{"given":"Xiaolong","family":"Wei","sequence":"first","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dombkowski","sequence":"additional","affiliation":[{"name":"Flow Cytometry Laboratory, Department of Pathology and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Meirelles","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Pieretti-Vanmarcke","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul P.","family":"Szotek","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry L.","family":"Chang","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic I.","family":"Preffer","sequence":"additional","affiliation":[{"name":"Flow Cytometry Laboratory, Department of Pathology and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Abdominal Imaging and Intervention Division and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"MacLaughlin","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia K.","family":"Donahoe","sequence":"additional","affiliation":[{"name":"Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,10,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0530291100"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3931"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2030"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603672103"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805012105"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.02.007"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.01.038"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0909-1010"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.374"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.04.003"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20006"},{"key":"e_1_3_3_12_2","first-page":"587","article-title":"The prognostic significance of angiogenesis in epithelial ovarian carcinoma","volume":"5","author":"Alvarez AA","year":"1999","unstructured":"AA Alvarez, HR Krigman, RS Whitaker, RK Dodge, GC Rodriguez, The prognostic significance of angiogenesis in epithelial ovarian carcinoma. 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