RT Journal Article
SR Electronic
T1 Human ovarian cancer ascites fluid contains a mixture of incompletely degraded soluble products of fibrin that collectively possess an antiangiogenic property
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 1536
OP 1544
DO 10.1136/ijgc-00009577-200607000-00007
VO 16
IS 4
A1 N. Jandu
A1 M. Richardson
A1 G. Singh
A1 H. Hirte
A1 M. W.C Hatton
YR 2006
UL http://ijgc.bmj.com/content/16/4/1536.abstract
AB Ovarian cancer ascites fluid (OCAF) displayed an antiangiogenic property in a chick chorioallantoic membrane (CAM) assay. This property was attributed in part to angiostatin although angiostatin-free OCAF retained a net antiangiogenic property. Recently, immunopurified fibrin(ogen) degradation products (FDPs) from malignant effusions of VX2 tumor–burdened rabbits exhibited antiangiogenic activity on the CAM. We questioned whether the FDPs of OCAF were also antiangiogenic. FDPs were immunopurified from individual OCAF samples, characterized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis /western blots, enzyme-linked immunosorbent assays, and CAM assays. FDPs of OCAFs consisted of soluble high molecular weight (MW) fragments (>200 kd; ∼40% of total FDPs), D-dimer (∼180 kd; ∼37%), fragment D (∼90 kd; ∼15%), and fragment E (∼50 kd; ∼8%); intact fibrinogen was absent. When applied to CAM surfaces (0.5–1.6 mg/10 mL), purified FDPs significantly reduced the area of chorionic capillaries from 90% (in controls) to 47% over a 48-h period; from CAM sections, capillary density was reduced from 60% (controls) to 26%. FDPs prepared from fibrinogen displayed a similar antiangiogenic effect. Further digestion of OCAF FDPs by human plasmin caused degradation of high MW fragments, releasing additional D-dimer, fragment D, and fragment E. Of the fibrinogen-related components, OCAF contained only soluble FDPs (including incompletely digested fibrin fragments). Collectively, these FDPs contributed to the net antiangiogenic property of ascites fluid.