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Updated: Jul 14, 2026
Assessment of Ovarian Cancer Spheroid Attachment and Invasion of Mesothelial Cells in Real Time
Published on: May 20, 2014
Binding of endostatin to human ovarian cancer cells inhibits cell attachment
Yumi Yokoyama1, S Ramakrishnan
1Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Abstract:
Endostatin, a C-terminal fragment of collagen type XVIII, is one of the well-characterized endogenous inhibitors of angiogenesis. Endostatin is known to bind integrin alpha(5)beta(1), which is upregulated on tumor endothelium. Most of the ovarian cancer cells express significant amounts of alpha(5)beta(1) integrin, which is important for ovarian cancer cells to attach to the peritoneal wall. Therefore we investigated whether endostatin could directly bind ovarian cancer cells and inhibit tumor cell attachment to extracellular matrix. Binding of endostatin to ovarian cancer cells was characterized by preincubation with function blocking antibodies to integrin subunits. These studies showed that ovarian cancer cell attachment to fibronectin-coated wells can be inhibited by alpha(5)beta(1) integrin specific antibodies as well as endostatin. Downregulation of integrin alpha(5) and beta(1) by siRNA abrogated the binding of OVCAR5 and human umbilical vein endothelial cell to endostatin. Although endostatin treatment did not affect ovarian cancer cell migration, treated cells failed to attach mouse peritoneal wall preparations. These studies suggest an extra-antiangiogenic role for endostatin, which can be used prevent peritoneal attachment and dissemination of ovarian cancer cells.
Insights
Endostatin, an angiogenesis inhibitor, prevents ovarian cancer cells from attaching to the peritoneal wall by binding to integrin alpha(5)beta(1). This suggests a novel therapeutic role beyond inhibiting tumor blood vessel growth.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Endostatin, derived from collagen type XVIII, is a known inhibitor of angiogenesis.
- Integrin alpha(5)beta(1) is upregulated on tumor endothelium and crucial for ovarian cancer cell adhesion to the peritoneum.
Purpose of the Study:
- To investigate if endostatin directly binds ovarian cancer cells.
- To determine if endostatin inhibits ovarian cancer cell attachment to the extracellular matrix and peritoneal wall.
Main Methods:
- Characterized endostatin binding to ovarian cancer cells using function-blocking antibodies against integrin subunits.
- Utilized siRNA to downregulate integrin alpha(5) and beta(1) expression.
- Assessed ovarian cancer cell attachment to fibronectin-coated wells and mouse peritoneal wall preparations.
Main Results:
- Endostatin inhibited ovarian cancer cell attachment to fibronectin, similar to alpha(5)beta(1) integrin antibodies.
- siRNA-mediated downregulation of integrin alpha(5) and beta(1) blocked endostatin binding.
- Endostatin treatment did not affect cell migration but prevented attachment to peritoneal tissue.
Conclusions:
- Endostatin exhibits an extra-antiangiogenic function by inhibiting ovarian cancer cell peritoneal attachment.
- Endostatin holds potential for preventing ovarian cancer metastasis and dissemination via peritoneal seeding.
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