Endostatin binding to ovarian cancer cells inhibits peritoneal attachment and dissemination

Yumi Yokoyama, Gerald Sedgewick, Sundaram Ramakrishnan

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Ovarian cancer cells use integrins to attach to the peritoneal wall. Integrin α5β1 is 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 α5β 1 and 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 α5 and β1 in ovarian cancer cells interfered with endostatin-mediated inhibition of peritoneal seeding. Furthermore, adenovirus-mediated in situ expression of endostatin either inside the peritoneum or by the ovarian tumor cells inhibited peritoneal seeding and dissemination in 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.

Original languageEnglish (US)
Pages (from-to)10813-10822
Number of pages10
JournalCancer Research
Volume67
Issue number22
DOIs
StatePublished - Nov 15 2007

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