Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells

Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells

Balance between pro-tumor and anti-tumor effects may be affected by molecular interactions within tumor microenvironment. On this basis we searched for molecular partners of ADAMTS-12, a secreted metalloprotease that shows both oncogenic and tumor-suppressive effects. Using its spacer region as a ba...

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Main Authors: Fontanil, Tania, Rúa, Susana, Llamazares, María, Moncada-Pazos, Angela, Quirós, Pedro M., García-Suórez, Olivia, Vega, Jose A., Sasaki, Takako, Mohamedi, Yamina, Esteban, Manuel M., Obaya, Alvaro J., Cal, Santiago
Format: Online
Language:English
Published: Impact Journals LLC 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012729/
id pubmed-4012729
recordtype oai_dc
spelling pubmed-40127292014-05-09 Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells Fontanil, Tania Rúa, Susana Llamazares, María Moncada-Pazos, Angela Quirós, Pedro M. García-Suórez, Olivia Vega, Jose A. Sasaki, Takako Mohamedi, Yamina Esteban, Manuel M. Obaya, Alvaro J. Cal, Santiago Research Paper Balance between pro-tumor and anti-tumor effects may be affected by molecular interactions within tumor microenvironment. On this basis we searched for molecular partners of ADAMTS-12, a secreted metalloprotease that shows both oncogenic and tumor-suppressive effects. Using its spacer region as a bait in a yeast two-hybrid screen, we identified fibulin-2 as a potential ADAMTS-12-interacting protein. Fibulins are components of basement membranes and elastic matrix fibers in connective tissue. Besides this structural function, fibulins also play crucial roles in different biological events, including tumorigenesis. To examine the functional consequences of the ADAMTS-12/fibulin-2 interaction, we performed different in vitro assays using two breast cancer cell lines: the poorly invasive MCF-7 and the highly invasive MDA-MB-231. Overall our data indicate that this interaction promotes anti-tumor effects in breast cancer cells. To assess the in vivo relevance of this interaction, we induced tumors in nude mice using MCF-7 cells expressing both ADAMTS-12 and fibulin-2 that showed a remarkable growth deficiency. Additionally, we also found that ADAMTS-12 may elicit pro-tumor effects in the absence of fibulin-2. Immunohistochemical staining of breast cancer samples allowed the detection of both ADAMTS-12 and fibulin-2 in the connective tissue surrounding tumor area in less aggressive carcinomas. However, both proteins are hardly detected in more aggressive tumors. These data and survival analysis plots of breast cancer patients suggest that concomitant detection of ADAMTS-12 and fibulin-2 could be a good prognosis marker in breast cancer diagnosis. Impact Journals LLC 2014-01-12 /pmc/articles/PMC4012729/ /pubmed/24457941 Text en Copyright: © 2014 Fontanil et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Fontanil, Tania
Rúa, Susana
Llamazares, María
Moncada-Pazos, Angela
Quirós, Pedro M.
García-Suórez, Olivia
Vega, Jose A.
Sasaki, Takako
Mohamedi, Yamina
Esteban, Manuel M.
Obaya, Alvaro J.
Cal, Santiago
spellingShingle Fontanil, Tania
Rúa, Susana
Llamazares, María
Moncada-Pazos, Angela
Quirós, Pedro M.
García-Suórez, Olivia
Vega, Jose A.
Sasaki, Takako
Mohamedi, Yamina
Esteban, Manuel M.
Obaya, Alvaro J.
Cal, Santiago
Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells
author_facet Fontanil, Tania
Rúa, Susana
Llamazares, María
Moncada-Pazos, Angela
Quirós, Pedro M.
García-Suórez, Olivia
Vega, Jose A.
Sasaki, Takako
Mohamedi, Yamina
Esteban, Manuel M.
Obaya, Alvaro J.
Cal, Santiago
author_sort Fontanil, Tania
title Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells
title_short Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells
title_full Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells
title_fullStr Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells
title_full_unstemmed Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells
title_sort interaction between the adamts-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells
description Balance between pro-tumor and anti-tumor effects may be affected by molecular interactions within tumor microenvironment. On this basis we searched for molecular partners of ADAMTS-12, a secreted metalloprotease that shows both oncogenic and tumor-suppressive effects. Using its spacer region as a bait in a yeast two-hybrid screen, we identified fibulin-2 as a potential ADAMTS-12-interacting protein. Fibulins are components of basement membranes and elastic matrix fibers in connective tissue. Besides this structural function, fibulins also play crucial roles in different biological events, including tumorigenesis. To examine the functional consequences of the ADAMTS-12/fibulin-2 interaction, we performed different in vitro assays using two breast cancer cell lines: the poorly invasive MCF-7 and the highly invasive MDA-MB-231. Overall our data indicate that this interaction promotes anti-tumor effects in breast cancer cells. To assess the in vivo relevance of this interaction, we induced tumors in nude mice using MCF-7 cells expressing both ADAMTS-12 and fibulin-2 that showed a remarkable growth deficiency. Additionally, we also found that ADAMTS-12 may elicit pro-tumor effects in the absence of fibulin-2. Immunohistochemical staining of breast cancer samples allowed the detection of both ADAMTS-12 and fibulin-2 in the connective tissue surrounding tumor area in less aggressive carcinomas. However, both proteins are hardly detected in more aggressive tumors. These data and survival analysis plots of breast cancer patients suggest that concomitant detection of ADAMTS-12 and fibulin-2 could be a good prognosis marker in breast cancer diagnosis.
publisher Impact Journals LLC
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012729/
_version_ 1612086170945060864

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