Lymphangioleiomyomatosis — a wolf in sheep’s clothing
Elizabeth P. Henske, Francis X. McCormack
Elizabeth P. Henske, Francis X. McCormack
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Science in Medicine

Lymphangioleiomyomatosis — a wolf in sheep’s clothing

Abstract

Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease of women. LAM is caused by mutations in the tuberous sclerosis genes, resulting in activation of the mTOR complex 1 signaling network. Over the past 11 years, there has been remarkable progress in the understanding of LAM and rapid translation of this knowledge to an effective therapy. LAM pathogenic mechanisms mirror those of many forms of human cancer, including mutation, metabolic reprogramming, inappropriate growth and survival, metastasis via blood and lymphatic circulation, infiltration/invasion, sex steroid sensitivity, and local and remote tissue destruction. However, the smooth muscle cell that metastasizes, infiltrates, and destroys the lung in LAM arises from an unknown source and has an innocent histological appearance, with little evidence of proliferation. Thus, LAM is as an elegant, monogenic model of neoplasia, defying categorization as either benign or malignant.

Authors

Elizabeth P. Henske, Francis X. McCormack

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Figure 4

Mechanisms of airspace enlargement in LAM.

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Mechanisms of airspace enlargement in LAM. Two models of airspace enlarg...
Two models of airspace enlargement in LAM are presented; these may not be mutually exclusive. (A) LAM cells secrete proteases including MMPs and cathepsin K, which degrade the extracellular matrix and induce apoptosis of alveolar epithelial cells. (B) LAM cells express lymphangiogenic growth factors, VEGF-C and VEGF-D, recruit lymphatic endothelial cells, drive the formation of lymphatic vascular channels and distort the lung architecture. Original magnification, ×200.