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LAM cells biology and lymphangioleiomyomatosis
open access
Abstract
Progressive lung tissue destruction in lymphangioleiomyomatosis (LAM) occurs as a result of excessive proliferation of LAM cells caused by a mutation in one of the tuberous sclerosis complex suppressor genes, TSC1 or TSC2. These cells show constitutive activation of the mammalian target of rapamycin (mTOR) pathway and many of the mTOR-related kinases such as Akt, Erk, S6K1 and S6. Phenotype of LAM cells differs considerably depending on their microenvironment. LAM cells show differences in morphology, size and expression of various factors depending on their location in the tumor or body fluids. The presence of LAM cells in blood, urine, bronchoalveolar lavage fluid (BALF), and chyle proves their ability to metastasis. Antigens of smooth muscle cells are expressed in most LAM cells. Some of these cells are immunoreactive with HMB-45 antibody, which is used for the immunohistochemical diagnosis of LAM. Receptors for estrogen and progesterone may also be expressed in these cells, which probably is associated with the fact that LAM occurs almost exclusively in women of childbearing age. LAM cells via increased production of metalloproteinases are involved in the destruction of the extracellular matrix, as well as the remodeling and damage of lung tissue. Sporadic LAM occurs extremely rarely. Therefore a good experimental model of this disease is necessary. To date, several animal and human cell lines, which both genetically and phenotypically resemble LAM cells, have been obtained. These cell lines, derived from LAM nodule or an angiomyolipoma, are usually characterized by a mutation of the TSC2 gene, expression of smooth muscle cell antigens such as a-smooth muscle actin (aSMA) or S6K1 and S6 protein hyperphosphorylation. Presently, there is no commercially available cell line representing a good model of LAM. A better understanding of LAM cell biology is necessary for creating a useful model in vitro for further exploration of both LAM pathomechanisms and more general mechanisms of carcinogenesis. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 1–10)
Abstract
Progressive lung tissue destruction in lymphangioleiomyomatosis (LAM) occurs as a result of excessive proliferation of LAM cells caused by a mutation in one of the tuberous sclerosis complex suppressor genes, TSC1 or TSC2. These cells show constitutive activation of the mammalian target of rapamycin (mTOR) pathway and many of the mTOR-related kinases such as Akt, Erk, S6K1 and S6. Phenotype of LAM cells differs considerably depending on their microenvironment. LAM cells show differences in morphology, size and expression of various factors depending on their location in the tumor or body fluids. The presence of LAM cells in blood, urine, bronchoalveolar lavage fluid (BALF), and chyle proves their ability to metastasis. Antigens of smooth muscle cells are expressed in most LAM cells. Some of these cells are immunoreactive with HMB-45 antibody, which is used for the immunohistochemical diagnosis of LAM. Receptors for estrogen and progesterone may also be expressed in these cells, which probably is associated with the fact that LAM occurs almost exclusively in women of childbearing age. LAM cells via increased production of metalloproteinases are involved in the destruction of the extracellular matrix, as well as the remodeling and damage of lung tissue. Sporadic LAM occurs extremely rarely. Therefore a good experimental model of this disease is necessary. To date, several animal and human cell lines, which both genetically and phenotypically resemble LAM cells, have been obtained. These cell lines, derived from LAM nodule or an angiomyolipoma, are usually characterized by a mutation of the TSC2 gene, expression of smooth muscle cell antigens such as a-smooth muscle actin (aSMA) or S6K1 and S6 protein hyperphosphorylation. Presently, there is no commercially available cell line representing a good model of LAM. A better understanding of LAM cell biology is necessary for creating a useful model in vitro for further exploration of both LAM pathomechanisms and more general mechanisms of carcinogenesis. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 1–10)
Keywords
lymphangioleiomyomatosis; LAM cells; mTOR; TSC1; TSC2; HMB-45; S6K1; αSMA
Title
LAM cells biology and lymphangioleiomyomatosis
Journal
Folia Histochemica et Cytobiologica
Issue
Article type
Review paper
Pages
1-10
Published online
2013-04-24
Page views
3886
Article views/downloads
4346
DOI
10.5603/FHC.2013.001
Bibliographic record
Folia Histochem Cytobiol 2013;51(1):1-10.
Keywords
lymphangioleiomyomatosis
LAM cells
mTOR
TSC1
TSC2
HMB-45
S6K1
αSMA
Authors
Irmina Grzegorek
Katarzyna Drozdz
Marzenna Podhorska-Okolow
Andrzej Szuba
Piotr Dziegiel