近日,，上海交通大學(xué)醫(yī)學(xué)院附屬仁濟(jì)醫(yī)院婦產(chǎn)科張殊博士在國際上首次成功從人卵巢癌組織中分離,、鑒定出人卵巢癌干細(xì)胞,，這一發(fā)現(xiàn)將使從根本上抑制卵巢癌的發(fā)生和發(fā)展成為可能。
新一期美國頂尖腫瘤研究雜志《癌癥研究》發(fā)表了這項(xiàng)研究結(jié)果,。
卵巢癌作為女性最常見的惡性腫瘤之一，雖然其發(fā)病率次于宮頸癌與子宮體癌,，但由于卵巢腫瘤深藏于盆腔,，患病初期很少有癥狀,，一旦出現(xiàn)腹痛、腹水等癥狀并確診為卵巢癌時(shí),，60%—70%的患者已屬晚期,。目前國外已著手卵巢惡性腫瘤早期診斷的研究，并普遍開展以手術(shù)為主的綜合治療,，但由于其繁多的病理分類,、組織結(jié)構(gòu)復(fù)雜等因素，治療效果一直不理想,。
腫瘤干細(xì)胞學(xué)說是一門新近發(fā)展起來的全新理論,，認(rèn)為腫瘤干細(xì)胞雖然只占全部腫瘤組織的極少數(shù)，但它卻是腫瘤形成,、發(fā)展和惡化的根源,。如何對腫瘤的干細(xì)胞進(jìn)行分子或者形態(tài)上的鑒定，并加以識別和分離,，是利用腫瘤干細(xì)胞來進(jìn)行癌癥治療的關(guān)鍵環(huán)節(jié),。
張殊博士在仁濟(jì)醫(yī)院婦產(chǎn)科林其德教授和狄文教授的悉心指導(dǎo)下，長期從事卵巢癌的臨床和科研工作,。在美國留學(xué)期間,，以她為首的研究團(tuán)隊(duì)，終于成功地從人卵巢癌組織中分離,、鑒定出人卵巢癌干細(xì)胞,，并發(fā)現(xiàn)卵巢癌干細(xì)胞擁有其特異的細(xì)胞表面標(biāo)志物CD44和CD117。這類細(xì)胞具備極強(qiáng)的自我更新,、增殖能力和多向分化潛能,，研究證實(shí)，100個(gè)卵巢癌干細(xì)胞即可在免疫缺陷鼠模型上形成人卵巢癌組織,。
隨著卵巢癌干細(xì)胞被成功“鎖定”,，今后科研人員有可能依據(jù)其分子標(biāo)志物，對患者進(jìn)行早期診斷和早期治療,。而以徹底消滅腫瘤干細(xì)胞為目標(biāo)的新化療方案,，也將給患者帶來治愈的新曙光。據(jù)介紹,，治療卵巢癌的另一個(gè)難題是,，多數(shù)卵巢癌患者對化療表現(xiàn)出極強(qiáng)的耐藥性，“卵巢癌干細(xì)胞的發(fā)現(xiàn),，為我們今后研發(fā)以徹底消滅腫瘤干細(xì)胞為指標(biāo)的新化療藥物提供了新的靶點(diǎn),。”張殊說，“通過探索有效的綜合治療方案，有望極大地降低卵巢癌的復(fù)發(fā)率,，從而提高治愈率和生存率,。”（生物谷Bioon.com）
生物谷推薦原始出處：
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: [email protected] .
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]
