近日，上海交通大学医学院附属仁济医院妇产科张殊博士在国际上首次成功从人卵巢癌组织中分离、鉴定出人卵巢癌干细胞，这一发现将使从根本上抑制卵巢癌的发生和发展成为可能。
新一期美国顶尖肿瘤研究杂志《癌症研究》发表了这项研究结果。
卵巢癌作为女性最常见的恶性肿瘤之一，虽然其发病率次于宫颈癌与子宫体癌，但由于卵巢肿瘤深藏于盆腔，患病初期很少有症状，一旦出现腹痛、腹水等症状并确诊为卵巢癌时，60%—70%的患者已属晚期。目前国外已着手卵巢恶性肿瘤早期诊断的研究，并普遍开展以手术为主的综合治疗，但由于其繁多的病理分类、组织结构复杂等因素，治疗效果一直不理想。
肿瘤干细胞学说是一门新近发展起来的全新理论，认为肿瘤干细胞虽然只占全部肿瘤组织的极少数，但它却是肿瘤形成、发展和恶化的根源。如何对肿瘤的干细胞进行分子或者形态上的鉴定，并加以识别和分离，是利用肿瘤干细胞来进行癌症治疗的关键环节。
张殊博士在仁济医院妇产科林其德教授和狄文教授的悉心指导下，长期从事卵巢癌的临床和科研工作。在美国留学期间，以她为首的研究团队，终于成功地从人卵巢癌组织中分离、鉴定出人卵巢癌干细胞，并发现卵巢癌干细胞拥有其特异的细胞表面标志物CD44和CD117。这类细胞具备极强的自我更新、增殖能力和多向分化潜能，研究证实，100个卵巢癌干细胞即可在免疫缺陷鼠模型上形成人卵巢癌组织。
随着卵巢癌干细胞被成功“锁定”，今后科研人员有可能依据其分子标志物，对患者进行早期诊断和早期治疗。而以彻底消灭肿瘤干细胞为目标的新化疗方案，也将给患者带来治愈的新曙光。据介绍，治疗卵巢癌的另一个难题是，多数卵巢癌患者对化疗表现出极强的耐药性，“卵巢癌干细胞的发现，为我们今后研发以彻底消灭肿瘤干细胞为指标的新化疗药物提供了新的靶点。”张殊说，“通过探索有效的综合治疗方案，有望极大地降低卵巢癌的复发率，从而提高治愈率和生存率。”（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer Res. 2008 68: 4311-4320. June 1, 2008. doi: 10.1158/0008-5472.CAN-08-0364
Identification and Characterization of Ovarian Cancer-Initiating Cells from Primary Human Tumors
Shu Zhang1,2, Curt Balch1,3,4, Michael W. Chan7, Hung-Cheng Lai8, Daniela Matei3,5,6, Jeanne M. Schilder3,6, Pearlly S. Yan9, Tim H-M. Huang9 and Kenneth P. Nephew1,3,4,6
1 Medical Sciences, Indiana University School of Medicine, Bloomington, Indiana; 2 Department of Obstetrics Gynecology, Ren Ji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; 3 Indiana University Simon Cancer Center; Departments of 4 Cellular and Integrative Physiology, 5 Medicine, and 6 Obstetrics Gynecology, Indiana University School of Medicine, Indianapolis, Indiana; 7 Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Ming-Hsiung, Chia-Yi, Taiwan, ROC; 8 Department of Obstetrics Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; and 9 Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio
Requests for reprints: Kenneth P. Nephew, Medical Sciences, 1001 East Third, Bloomington, IN 47405. Phone: 812-855-9445; Fax: 812-855-4436; E-mail: knephew@indiana.edu .
Key Words: ovarian cancer • cancer stem cells • drug resistance
The objective of this study was to identify and characterize a self-renewing subpopulation of human ovarian tumor cells (ovarian cancer-initiating cells, OCICs) fully capable of serial propagation of their original tumor phenotype in animals. Ovarian serous adenocarcinomas were disaggregated and subjected to growth conditions selective for self-renewing, nonadherent spheroids previously shown to derive from tissue stem cells. To affirm the existence of OCICs, xenoengraftment of as few as 100 dissociated spheroid cells allowed full recapitulation of the original tumor (grade 2/grade 3 serous adenocarcinoma), whereas >105 unselected cells remained nontumorigenic. Stemness properties of OCICs (under stem cell–selective conditions) were further established by cell proliferation assays and reverse transcription–PCR, demonstrating enhanced chemoresistance to the ovarian cancer chemotherapeutics cisplatin or paclitaxel and up-regulation of stem cell markers (Bmi-1, stem cell factor, Notch-1, Nanog, nestin, ABCG2, and Oct-4) compared with parental tumor cells or OCICs under differentiating conditions. To identify an OCIC cell surface phenotype, spheroid immunostaining showed significant up-regulation of the hyaluronate receptor CD44 and stem cell factor receptor CD117 (c-kit), a tyrosine kinase oncoprotein. Similar to sphere-forming OCICs, injection of only 100 CD44+CD117+ cells could also serially propagate their original tumors, whereas 105 CD44–CD117– cells remained nontumorigenic. Based on these findings, we assert that epithelial ovarian cancers derive from a subpopulation of CD44+CD117+ cells, thus representing a possible therapeutic target for this devastating disease. [Cancer Res 2008;68(11):4311–20]
