FIBRINOGEN INFLUX AND FIBRIN ACCUMULATION IN ASCITES TUMORS

J Nagy, H Devorak
1987 DIET   unpublished
Fibrin gel matrix organizes solid tumors into discrete cell nests and providesa provisional matrix for mature stroma generation. Fibrin deposits result fromlocal extravasation of plasma fibrinogen followed by extravascular coagulationand crosslinking. Unlike solid tumors, ascites tumor cells in body cavities grow in suspension, and are not envelopedin fibrin gel. The lack of fibrin gel in ascites tumors has several possible explanations: 1. Peritoneal wall blood vessels are impermeable to
more » ... les as large as fibrinogen. 2. Fibrinogen leaks from peritoneal vessels, but is clotted to fibrin and never reaches the peritoneal cavity. 3. Fibrinogen leaks from vessels, reaches the peritoneal cavity, and is rapidly degraded. To distinguish among these possibilities we investigated the permselective properties of the peritoneal wall. We measured the influx of intravenously (iv) administered, fluorescein-labeled dextrans (FITC-D) of varying size into the peritonea of normal and tumor or inflammatory ascites-bearing mice and guinea pigs. FITC-D of MW 70-5,000 kD leaked from vessels and ∽ 10-fold more entered MOT or TA3/St tumor-associated or serotonin-induced inflammatory ascites than normal peritonea. In tumor bearing animals, 3-20% of injected FITC-D entered the peritoneum within 15-30 min., all of it intact by gel exclusion chromatography. We also investigated the influx of fluorescein-labeled fibrinogen (FITC-F). At 30-60 min after iv injection, FITC-F hadextravasated into the peritoneal wall as judged by fluorescence microscopy (tumor bearing ≫ normal animals). Moreover, monoclonal antibodies reactivewith fibrin, but not fibrinogen, stained such deposits by immunohistochemistry in guinea pigs bearing line 1 or line 10 ascites tumors. Following iv injection of 125l-fibrinogen, as much as 11% of injected radioactivity accumulated in tumor ascites fluid over1-3 hrs (versus ∽1% in normal controls). In both, only ∽half was clottableand 3040% was of low MW (≤.10 kD). In contrast, iv 125I-albumin also entered the peritoneal cavity at an enhanced rate but showed no evidence of degradation. We conclude that fibrinogen extravasates from peritoneal vessels,thatleakage is increased in ascites tumor-bearing animals, and that fibrinogen clots, at least in part, before it enters the peritoneal cavity. Also, fibrinogen undergoes selective degradation and much of the fibrinogen that does enter the peritoneum represents degradation products of fibrinogen/fibrin. The resulting lack of peritoneal fibrin gel matrixfavors the suspension pattern of ascites, as compared with solid tumor growth.
doi:10.1055/s-0038-1643668 fatcat:o6qmb2q5rbaovba57gn5cgyriu