Cellular senescence of angiofibroma stroma cells from patients with tuberous sclerosis

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characte rized by epilepsy, mental retardation and hamartomatous lesions in multiple organs. It has been shown that the genes responsible for TSC, TSC1 and TSC 2, act as tumor suppressors. but the mechanism of hamartomatous growth in s everal tissues is not completely understood. The TSC hamartomas are essenti ally benign and they rarely progress to malignant tumors. In this report, w e cultured the angiofibroma stroma cells of three adult TSC patients and co mpared these cells with normal skin fibroblasts for their proliferative cap acity, cell morphology and mitotic cycle using a stain for microtubules and the expression of the senescent associated beta-galactosidase (SA beta-Gal ). Cultured angiofibroma stroma cells from TSC patients displayed several c haracteristics observed in human senescent fibroblasts; a low proliferative capacity, an increase in cell size, increased binucleated cells in associa tion with abnormal cytokinesis and increased SA beta-Gal positives. Growth of facial angiofibromas in TSC may be caused by a gain in enhanced sensitiv ity toward some of the potential mitogens and forced multiplication without loss of the cellular senescent program; this may be the reason why TSC ham artomas rarely progress to malignancy and why the growths are limited to a finite size. (C) 1999 Published by Elsevier Science B.V. All rights reserve d.