来自美国密执安州立大学、宾西法尼亚州立大学,希腊和意大利的大学的研究小组,利用激光技术从21例卵巢肿瘤和4例正常卵巢组织样本分离出血管细胞,进而确定血管细胞表现的基因。
这项结果鉴别了在癌组织血管中大量存在,但在正常组织血管中不存在的70多种生物标记。研究人员继续深入研究之前与肿瘤血管无关的12种生物标记。这项研究报告刊载于3月1日的Journal of Clinical Oncology。
研究作者Ronald Buckanovich博士表示,这些基因中有一部分在肿瘤血管中高度表现,因此可以成为病人生存的预后因子。研究人员认为当这些基因高度表现时,表示肿瘤的血管可以有效地新生,因此更具侵略性。
这项研究分析了大量的肿瘤血管系统或血管、剖面的样本。尽管这次分离的许多基因都已经显示与其它类型癌有关,但还是发现了一些新的生物标记。
另外,研究人员也发现几种于卵巢肿瘤中表现的生物标记,在正常卵巢或其它健康器官中并未表现。研究人员同时发现这些生物标记在血管生长的正常生殖组织中不存在,例如胎盘或子宫内膜。因此可以确定这些生物标记具肿瘤之特异性。
如果这些生物标记确实对卵巢肿瘤具有特异性,未来将可以发展出专门破坏肿瘤血管而使肿瘤无法生长的药物。
(资料来源 : Bio.com)
部分英文原文:
Journal of Clinical Oncology, Vol 25, No 7 (March 1), 2007: pp. 852-861
© 2007 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2006.08.8583
Tumor Vascular Proteins As Biomarkers in Ovarian Cancer
Ronald J. Buckanovich, Dimitra Sasaroli, Anne O'Brien-Jenkins, Jeffrey Botbyl, Rachel Hammond, Dionysios Katsaros, Raphael Sandaltzopoulos, Lance A. Liotta, Phyllis A. Gimotty, George Coukos
From the Center for Research on Reproduction and Women's Health, Abramson Family Cancer Research Institute, Department of Medicine Division of Hematology-Oncology, and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA; University of Michigan, Ann Arbor, MI; Center for Applied Proteomics and Molecular Medicine, George Mason University, Fairfax, VA; Department of Obstetrics and Gynecology, University of Turin, Turin, Italy; and Molecular Biology and Genetics Program, Democritus University of Thrace, Komotini, Greece
Address reprint requests to George Coukos, MD, PhD, 1315 BRB II/III, 421 Curie Blvd, Philadelphia, PA, 19104; e-mail: gcks@mail.med.upenn.edu
Purpose: This study aimed to identify novel ovarian cancer biomarkers and potential therapeutic targets through molecular analysis of tumor vascular cells.
Methods: Immunohistochemistry-guided laser-capture microdissection and genome-wide transcriptional profiling were used to identify genes that were differentially expressed between vascular cells from human epithelial ovarian cancer and healthy ovaries. Tumor vascular markers (TVMs) were validated through quantitative real-time polymerase chain reaction (qRT-PCR) of immunopurified tumor endothelial cells, in situ hybridization, immunohistochemistry, and Western blot analysis. TVM expression in tumors and noncancerous tissues was assessed by qRT-PCR and was profiled using gene expression data.
Results: We identified a tumor vascular cell profile of ovarian cancer that was distinct from the vascular profile of normal ovary and other tumors. We validated 12 novel ovarian TVMs. These were expressed by immunopurified tumor endothelial cells and localized to tumor vasculature. select TVMs were found to be specifically expressed in ovarian cancer and were absent in all normal tissues tested, including female reproductive tissues with physiologic angiogenesis. Many ovarian TVMs were expressed by a variety of other solid tumors. Finally, overexpression of any one of three ovarian TVMs by vascular cells was associated with decreased disease-free interval (all P < .005).
Conclusion: We have identified for the first time the molecular profile of ovarian tumor vasculature. We demonstrate that TVMs may serve as potential biomarkers and molecular targets for ovarian cancer and a variety of other solid tumors.
Supported by National Institutes of Health (NIH) Grant No. R01 CA098951; National Cancer Institute (NCI) Ovarian Cancer Specialized Program of Research Excellence (SPORE) Grant No. P50-CA083638; US Army Medical Research and Materiel Command Grant No. OC-050314; and the Marcia and Philip Rothblum Foundation. R.J.B. was supported by NIH/National Institute of Child Health and Human Development Grant No. K12-HD43459 and the Ovarian Cancer Research Fund. The laser-capture microdissection facility was supported by a generous grant by the Fannie Rippel Foundation.
R.J.B and D.S. contributed equally to this work.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.