Vascular endothelial growth factor production and regulation in rodent andhuman pituitary tumor cells in vitro

Angiogenesis, the formation of a new blood supply, is an essential step in tumorigenesis. Although vascular endothelial growth factor (VEGF) is known to be a very potent angiogenic factor in most solid tumors, little is known about its production and regulation in pituitary adenomas. We have investi gated basal and stimulated VEGF production by rodent pituitary tumor cells (mouse corticotrope AtT20, rat lactosomatotrope GH3, mouse gonadotrope alph a T3-1 and mouse folliculostellate TtT/GF cells), and by hormone-inactive ( 27), corticotrope (9), lactotrope (3) and somatotrope (21) human pituitary adenoma cell cultures. All 4 pituitary cell lines secreted VEGF, which in t he case of AtT20, GH3 and TtT/GF cells was inhibited by approximately 50% b y dexamethasone. TtT/GF cells were the most responsive to the different sti muli used since basal values were augmented by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), interleukin-6 (IL-6), transforming gr owth factor-cc (TGF-a), IGF-I and the somatostatin analogue ocreotide. Howe ver, in GH3, AtT20 and aT3-1 cells, basal VEGF levels where not enhanced wi th any of the stimuli tested. The majority of the human adenomas tested (92 %) basally secreted measurable VEGF which was inhibited by dexamethasone in most cases (84%). VEGF levels were increased in hormone inactive adenomas, somatotrope tumors and prolactinomas by TGF-alpha, PACAP-38, and 17 beta - estradiol, respectively. In conclusion, pituitary tumor cells are capable o f producing VEGF which may be involved in tumoral angiogenesis. Our results concerning the suppression of VEGF by dexamethasone suggest that glucocort icoids may have anti-angiogenic properties and therefore therapeutic releva nce for the treatment of pituitary adenomas.