High angiogenic activity in cells isolated from cystic hygroma - Role of bFGF

Background: Cystic hygromas are characterized by a proliferation of small v essels and lymphatics with intervening fibrous tissue. Studies have shown m alignant tumors and some benign neoplasms are dependent on angiogenesis, th e induction of new capillaries from preexisting vessels. Growth and progres sion of these tumors are associated with a disturbance in the balance of an giogenic inducers and inhibitors. We have postulated that cells derived fro m cystic hygromas are angiogenic due to secretion of higher levels of angio genic inducers that promote vascular proliferation. Design: A large cystic mass was surgically removed and a portion of the ste rile tumor was immediately placed in the medium. The tissue was minced, was hed in phosphate-buffered saline, and grown to near confluence. Conditioned medium was collected under serum-free conditions after 48 hours. Secreted proteins were concentrated. quantitated, and analyzed in an in vitro endoth elial cell migration assay and by Western blot. Antibody to factor VIII-rel ated antigen was performed to confirm endothelial cell origin of the cultur ed cells. Main Outcome Measures: In vitro angiogenic activity of secreted proteins in a capillar) endothelial migra tion assay was tested by using blocking anti bodies to angiogenic inducer, basic fibroblast growth factor, and angiogeni c inhibitor, thrombospondin-l. Total protein levels of thrombospondin-l wer e determined by Western blot. Results: Cells isolated from cystic hygroma are angiogenic in vitro and thi s angiogenic activity is due to secretion of high levels of angiogenic indu cer, basic fibroblast growth factor, and lower levels of naturally occurrin g angiogenic inhibitor, thrombospondin-l. Conclusions: Cystic hygromas may represent another neoplasm dependent on an giogenesis. The angiogenic activity is due in part to elevated levels of po tent angiogenic inducer, basic fibroblast growth factor. Anti-angiogenic th erapy directed at the endothelial cell may help suppress the growth of cyst ic hygromas.