美国研究人员18日报告说，他们通过在实验室模拟卵巢癌形成过程发现，卵巢癌可能始自输卵管，而非卵巢。
美国达纳－法伯癌症研究所研究人员在新一期美国《国家科学院学报》上报告说，他们在一些携带卵巢癌基因的女性输卵管组织中发现了“可能发展为严重癌症的细胞”，因此他们决定在实验室内模拟卵巢癌形成过程。
输卵管是从女性卵巢连通至阴道的管道，包括中输卵管和侧输卵管，卵子经此管道排出。研究人员提取一些输卵管细胞并改变它们的基因片段，使其能够像癌细胞那样分裂。实验显示，和真正的癌细胞一样，这些“人造”癌细胞可以迅速增殖，并离开原发组织，在其他组织内生长。如果把这些“人造”癌细胞植入动物体内，它们能够催生在结构、行为和基因构成上与人类严重卵巢癌极其类似的肿瘤。
报告作者之一龙尼·德拉普金说，这一研究表明卵巢癌可能来自输卵管细胞，它将有助于寻找新的卵巢癌生物标记物，为今后的卵巢癌治疗提供了新的思路。
卵巢癌是女性面临的第5大癌症。据统计，全球每年新增大约20万卵巢癌患者，并有11．5万患者死亡。（生物谷Bioon.com）
生物谷推荐原文出处：
Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1017300108
Modeling high-grade serous ovarian carcinogenesis from the fallopian tube
Alison M. Karsta, Keren Levanona,1, and Ronny Drapkina,b,2
Abstract
High-grade serous ovarian carcinoma (HGSOC) is a lethal disease for which improved screening and treatment strategies are urgently needed. Progress in these areas is impeded by our poor understanding of HGSOC pathogenesis. Most ovarian cancer research is based on the hypothesis that HGSOC arises from ovarian surface epithelial cells. However, recent studies suggest that >50% of high-grade serous carcinomas involving the ovary likely arise from fallopian tube epithelium. Therefore, limiting HGSOC research to modeling based on ovarian surface epithelium alone is inadequate. To address the need for a fallopian tube–based model of HGSOC, we have developed a system for studying human fallopian tube secretory epithelial cell (FTSEC) transformation. Our model is based on (i) immortalization of FTSECs isolated from primary samples of normal, nondiseased human fallopian tubes, (ii) transformation of FTSECs with defined genetic elements, and (iii) xenograft-based tumorigenic assays. We use our model to show that FTSECs immortalized with human telomerase reverse transcriptase (hTERT) plus SV40 large T and small T antigens are transformed by either oncogenic Ras (H-RasV12) or c-Myc expression, leading to increased proliferation, clonogenicity, and anchorage-independent growth. Additionally, we demonstrate that FTSECs remain susceptible to c-Myc–mediated transformation in the absence of viral oncoproteins, by replacing SV40 large T and small T antigens with sh-p53, mutant CDK4 (CDK4R24C), and sh-PP2A-B56γ. Importantly, all transformed FTSECs gave rise to high-grade Müllerian carcinomas that were grossly, histologically, immunophenotypically, and genomically similar to human HGSOC. With this model, we will now be able to assess the transformative effects of specific genetic alterations on FTSECs in order to characterize their respective roles in HGSOC development.
