生物谷报道：法国国家科研中心的研究人员日前报告说，他们此前为治疗艾滋病而合成的一种分子能够阻断肿瘤细胞的生长，并破坏其周围血管的生成。这一研究为肿瘤治疗提供了新思路。
科研人员早在1998年就合成了这种名为HB-19的分子，当时是为了研究艾滋病的疗法，不过最近他们发现，HB-19分子对于清除肿瘤细胞表面的核仁素具有特殊功效。
核仁素是真核细胞核仁中的一种蛋白质，它直接或间接参与细胞的繁殖和生长，具有十分重要的作用。
负责这项研究的阿拉·霍瓦尼西安表示，癌症的出现需要两个因素：其一是肿瘤细胞增殖，其二是为肿瘤细胞提供营养的血管，而这两者的生长都与核仁素有关。HB-19分子可与核仁素结合，进入细胞质中，核仁素随后会发生分解，从而阻断癌症发生的过程。
为了证明这一方法的有效性，研究人员将人的肿瘤细胞植入实验鼠体内，然后给它注射了含有HB-19分子的针剂。实验结果显示，肿瘤的生长得到了显著抑制，在一些比较好的情况下，肿瘤细胞甚至被全部杀死。
这一成果发表在新一期美国《公共科学图书馆·综合》（PLoS ONE）杂志上，并有望于2009年进入临床试验阶段。（生物谷www.bioon.com）
生物谷推荐原始出处：
PLoS ONE，doi:10.1371/journal.pone.0002518，Damien Destouches，Ara G. Hovanessian
Suppression of Tumor Growth and Angiogenesis by a Specific Antagonist of the Cell-Surface Expressed Nucleolin
Damien Destouches1#, Diala El Khoury2#, Yamina Hamma-Kourbali1, Bernard Krust2, Patricia Albanese1, Panagiotis Katsoris3, Gilles Guichard4, Jean Paul Briand4, José Courty1, Ara G. Hovanessian2*
1 CNRS UMR 7149, Université Paris-Est, Créteil, France2 CNRS UPR 2228, Université Paris Descartes, Paris, France3 Laboratory of Molecular Pharmacology, University of Patras, Patras, Greece4 CNRS UPR 9021, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France
Abstract
Background
Emerging evidences suggest that nucleolin expressed on the cell surface is implicated in growth of tumor cells and angiogenesis. Nucleolin is one of the major proteins of the nucleolus, but it is also expressed on the cell surface where is serves as a binding protein for variety of ligands implicated in cell proliferation, differentiation, adhesion, mitogenesis and angiogenesis.
Methodology/Principal Findings
By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, here we show that the growth of tumor cells and angiogenesis are suppressed in various in vitro and in vivo experimental models. HB-19 inhibited colony formation in soft agar of tumor cell lines, impaired migration of endothelial cells and formation of capillary-like structures in collagen gel, and reduced blood vessel branching in the chick embryo chorioallantoic membrane. In athymic nude mice, HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in nude mice, and in some cases eliminated measurable tumors while displaying no toxicity to normal tissue. This potent antitumoral effect is attributed to the direct inhibitory action of HB-19 on both tumor and endothelial cells by blocking and down regulating surface nucleolin, but without any apparent effect on nucleolar nucleolin.
Conclusion/Significance
Our results illustrate the dual inhibitory action of HB-19 on the tumor development and the neovascularization process, thus validating the cell-surface expressed nucleolin as a strategic target for an effective cancer drug. Consequently, the HB-19 pseudopeptide provides a unique candidate to consider for innovative cancer therapy.
