Hormonal manipulation of meningiomas in vitro

Abstract

✓ Speculation that meningiomas are subject to endocrine influence is supported by their higher incidence in women, reports of exacerbation of symptoms during pregnancy, and the discovery that these tumors harbor progesterone- and estrogen-binding proteins. To evaluate if these properties could be exploited therapeutically, specimens from three convexity meningiomas were used for estrogen- and progesterone-binding protein assays and establishment of tissue cultures. Each tumor (designated A, B, and C, respectively) was grown in experimental media containing 7.5 × 10−5 to 10−12 M 17β-estradiol, 2.5 × 10−4 to 10−12 M progesterone, 10−7 to 10−9 M tamoxifen (an estrogen antagonist), and 10−6 to 10−10 M RU486 (a progesterone antagonist). After incubation, cell growth was compared to control preparations by counting the meningioma cells present in each medium. Tumors A, B, and C contained estrogen-binding proteins of 8.45, 13.6, and 26.9 fmol/mg cytosol protein and progesterone-binding proteins of 210, 130, and 126 fmol/mg cytosol protein, respectively. The media containing 17β-estradiol and progesterone caused 21% to 36% growth stimulation in Tumors A and B. In Tumor A, the addition of tamoxifen stimulated growth by 35%, while it caused only transient stimulation in Tumor B and had no effect on Tumor C. RU486, the progesterone antagonist, caused inhibition of cell growth in all three tumors, ranging from 18% to 36%. These data suggest that selected meningiomas are subject to hormonal influence in vitro. The inhibition of meningioma growth in vitro by the antiprogesterone, RU486, has not been previously reported, and serves to encourage further development of alternative modes of therapy for recurrent and unresectable meningiomas.