Metastasis of benign tumor cells in tuberous sclerosis complex
Article first published online: 8 OCT 2003
Copyright © 2003 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 38, Issue 4, pages 376–381, December 2003
How to Cite
Henske, E. P. (2003), Metastasis of benign tumor cells in tuberous sclerosis complex. Genes Chromosom. Cancer, 38: 376–381. doi: 10.1002/gcc.10252
- Issue published online: 14 OCT 2003
- Article first published online: 8 OCT 2003
- Manuscript Accepted: 8 APR 2003
- Manuscript Received: 4 FEB 2003
Lymphangiomyomatosis (LAM) is a life-threatening lung disease affecting almost exclusively young women. Histologically, LAM is characterized by the diffuse, bilateral proliferation of abnormal smooth muscle cells and cystic degeneration of the lung parenchyma. LAM can occur as an isolated disorder (sporadic LAM), or in women with tuberous sclerosis complex (TSC-LAM). Patients with both sporadic LAM and TSC-LAM often have benign renal angiomyolipomas. The smooth muscle cells within the angiomyolipomas are very similar to the smooth muscle cells in pulmonary LAM. Genetic data suggest that pulmonary LAM is the result of a highly unusual disease mechanism: the metastasis of benign cells. If LAM is the result of metastasis, it is remarkable that the metastasis occurs in women, but not in men. In this review, I discuss the genetic data supporting this metastatic model for LAM. The implications of the model for the functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively, will also be considered. Hamartin and tuberin may play functional roles in the suppression of cell migration and/or metastasis, possibly through their regulation of the small GTPase Rho. © 2003 Wiley-Liss, Inc.