LAM/TSC cell migration to uterus in an experimental model of lymphangioleiomyomatosis. Regulation by anti-epidermal growth factor receptor antibody and rapamycin
Articolo
Data di Pubblicazione:
2014
Citazione:
LAM/TSC cell migration to uterus in an experimental model of lymphangioleiomyomatosis. Regulation by anti-epidermal growth factor receptor antibody and rapamycin / E. Lesma, E. Chiaramonte, S. Ancona, A.M. Di Giulio, A. Gorio. - (2014), pp. 1-6. [Epub ahead of print] [10.4172/2157-7099.S4-007]
Abstract:
Lymphangioleiomyomatosis (LAM) is a rare lung disease affecting almost exclusively women, characterized by
the invasion and abnormal proliferation of smooth muscle-like cells in pulmonary parenchyma and axial lymphatics.
LAM cells bear mutations in Tuberous Sclerosis Complex (TSC) genes. It has been hypothesized that uterus might
be the primary site of origin and one of the most frequent metastatic or disseminated site of LAM cells. We developed
a mouse model to study the migratory and invasive properties of human LAM/TSC cells to the uterus. We also
examined the action of rapamycin and anti-Epidermal Growth Factor Receptor (EGFR) antibody.
LAM/TSC cells were endonasally administered to 3 week old immunodeficient female nude mice. 5 months later
mice were divided in 4 groups: control, LAM/TSC cell-administered mice, LAM/TSC cell-administered mice treated
with rapamycin, and LAM/TSC cell-administered mice treated with anti-EGFR antibody. Drugs were administered for
one months. Uteri were analysed for the presence of human LAM/TSC cells by COX IV antibody, lymphangiogenesis
by LYVE 1 expression and angiogenesis by counting blood vessels.
LAM/TSC cells migrated to the uterus without causing any morphological lesion. Interestingly, LAM/TSC cells
increased the number of blood vessels while did not cause any alteration in lymphatics vessels. Anti-EGFR antibody
and rapamycin reduced the number of human LAM/TSC and counteracted the proliferation of blood vessels in
uteri. Although both drugs did not change the expression of LYVE 1, localization of lymphatics was mainly in the
perimetrium after drug treatment.
Our data describe the strong invasive capability of human LAM/TSC cells which migrated to the uterus. LAM/
TSC cells presence is accompanied by increased angiogenesis. Anti-EGFR antibody and rapamycin were effective
in reducing the LAM/TSC cell number and blood vessel proliferation.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Tuberous sclerosis complex ; anti-EGFR antibody ; rapamcyin Lymphangioleiomyomatosis; Migration ; Uterus ; tuberin-null cells ; mouse mode
Elenco autori:
E. Lesma, E. Chiaramonte, S. Ancona, A.M. Di Giulio, A. Gorio
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