Endostatin binding to ovarian cancer cells inhibits peritoneal attachment and dissemination.
Endostatin binding to ovarian cancer cells inhibits peritoneal attachment and dissemination.
复制标题
内皮抑素与卵巢癌细胞的结合抑制腹膜附着和扩散。
DOI：
10.1158/0008-5472.can-07-0172
复制
发表时间：
2007
期刊：
影响因子：
11.2
通讯作者：
Ramakrishnan,S
中科院分区：
文献类型：
--
作者：
Yokoyama,Yumi;Sedgewick,Gerald;Ramakrishnan,S
卵巢癌细胞利用整合素附着在腹膜壁上。整合素α5β 1也是血管生成抑制剂内皮抑素的靶点。因此，研究了内皮抑制素竞争性抑制腹膜肿瘤细胞接种的能力。发展了一种成像方法来确定卵巢癌细胞腹膜播散的早期阶段。利用该方法发现内皮抑素通过整合素α5β 1与卵巢癌细胞结合，有效抑制血管黏附。尽管血管抑素和内皮抑素都是肿瘤血管生成的有效抑制剂，但只有内皮抑素才能阻断腹膜附着和血管结合。下调卵巢癌细胞整合素α 5和β 1的表达干扰内皮抑素介导的腹膜种植抑制此外，腺病毒介导的内皮抑素在腹膜内或卵巢肿瘤细胞中的原位表达抑制了体内腹膜种植和传播。内皮抑制素治疗也防止原发性卵巢癌细胞附着到小鼠腹膜壁。这些研究表明，内皮抑制素可以抑制卵巢癌细胞的腹膜传播，并提高腹膜内表达内皮抑制素，以减少复发的可能性的副内皮机制。[Cancer Res 2007;67（22）：10813-22]
Ovarian cancer cells use integrins to attach to the peritoneal wall. Integrin α5β1is also the target for the angiogenesis inhibitor, endostatin. Therefore, the ability of endostatin to competitively inhibit tumor cell seeding of the peritoneum was investigated. An imaging method was developed to determine early phases of peritoneal dissemination of ovarian cancer cells. Using this method, endostatin was found to bind ovarian cancer cells through integrin α5β1and inhibit vessel cooption efficiently. Although both angiostatin and endostatin are potent inhibitors of tumor angiogenesis, peritoneal attachment and vessel cooption was blocked only by the endostatin. Knocking down the expression of integrins α5and β1in ovarian cancer cells interfered with endostatin-mediated inhibition of peritoneal seeding. Furthermore, adenovirus-mediatedin situexpression of endostatin either inside the peritoneum or by the ovarian tumor cells inhibited peritoneal seeding and disseminationin vivo. Endostatin treatment also prevented primary ovarian cancer cells from attaching to mouse peritoneal wall. These studies show a paraendothelial mechanism by which endostatin can inhibit peritoneal dissemination of ovarian cancer cells and raises the possibility of intraperitoneal expression of endostatin to reduce recurrence. [Cancer Res 2007;67(22):10813–22]