Lymphangioleiomyomatosis and <em>TSC2<sup>-/-</sup></em> Cells

Thomas Darling

Gustavo Pacheco–Rodriguez

Alfredo Gorio

Elena Lesma

Cheryl Walker

Joel Moss

^{Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.}

^{Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.}

^{Laboratory of Pharmacology, Department of Medicine, Surgery and Dentistry, Faculty of Medicine, Università degli Studi di Milano, Milan, Italy.}

^{Clinical Pharmacology, IRCCS Humanitas, Milan, Italy.}

^{Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas.}

^{Corresponding author.}

Address correspondence to: Thomas N. Darling, M.D., Ph.D., Department of Dermatology, Uniformed Services University of Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814. E-mail:lim.shusu@gnilradt

Abstract

The cells comprising pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipomas (AMLs) are heterogeneous, with variable mixtures of cells exhibiting differentiation towards smooth muscle, fat, and vessels. Cells grown from LAM and AMLs have likewise tended to be heterogeneous. The discovery that LAM and AMLs contain cells with mutations in the TSC1 or TSC2 genes is allowing investigators to discriminate between “two-hit” cells and neighboring cells, providing insights into disease pathogenesis. In rare cases, it has been possible to derive cells from human tumors, including AMLs and TSC skin tumors that are highly enriched for TSC2^-/- cells. Cells derived from an Eker rat uterine leiomyoma (ELT3 cells) are Tsc2-null and these have been used in a rodent cell models for LAM. Further improvements in the ability to reliably grow well-characterized TSC2^-/- cells from human tumors are critical to developing in vitro and in vivo model systems for studies of LAM pathogenesis and treatment.

Abstract

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