open access

Vol 51, No 1 (2013)
Review paper
Submitted: 2013-04-28
Published online: 2013-04-24
Get Citation

LAM cells biology and lymphangioleiomyomatosis

Irmina Grzegorek, Katarzyna Drozdz, Marzenna Podhorska-Okolow, Andrzej Szuba, Piotr Dziegiel
DOI: 10.5603/FHC.2013.001
·
Folia Histochem Cytobiol 2013;51(1):1-10.

open access

Vol 51, No 1 (2013)
REVIEW
Submitted: 2013-04-28
Published online: 2013-04-24

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)

Get Citation

Keywords

lymphangioleiomyomatosis; LAM cells; mTOR; TSC1; TSC2; HMB-45; S6K1; αSMA

About this article
Title

LAM cells biology and lymphangioleiomyomatosis

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 51, No 1 (2013)

Article type

Review paper

Pages

1-10

Published online

2013-04-24

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

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl