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Title: Lymphangioleiomyomatosis biomarkers linked to lung metastatic potential and cell stemness
Author: Ruiz de Garibay, Gorka
Herranz, Carmen
Llorente, Alicia
Boni, Jacopo
Serra-Musach, Jordi
Mateo González, Francesca
Aguilar, Helena
Gómez Baldó, Laia
Petit, Anna
Vidal-Bel, August
Climent, Fina
Hernández-Losa, Javier
Cordero, Alex
González Suárez, Eva
Sanchez-Mut, Jose Vicente
Esteller, Manel
Llatjós, Roger
Varela Rodríguez, Mar
López, José Ignacio
García, Nadia
Extremera, Ana I.
Gumà i Garcia, Anna Maria
Ortega, Raúl
Pla Farnós, María Jesús
Fernández, Adela
Pernas, Sònia
Falo, Catalina
Morilla, Idoia
Campos, Miriam
Gil, Miguel
Román, Antonio
Molina Molina, María
Ussetti, Piedad
Laporta, Rosalía
Valenzuela, Claudio
Ancochea Bermúdez, Julio
Xaubet Mir, Antonio
Casanova, Álvaro
Pujana Genestar, M. Ángel
Keywords: Càncer de mama
Marcadors tumorals
Càncer de pulmó
Breast cancer
Tumor markers
Lung cancer
Issue Date: 13-Jul-2015
Publisher: Public Library of Science (PLoS)
Abstract: Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2015, vol. 10, num. 7, p. e0132546
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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