Radiation and Stemness Phenotype May Influence Individual Breast Cancer Outcomes: The Crucial Role of MMPs and Microenvironment

Breast cancer is the most common cancer in women. Radiotherapy (RT) is one of the mainstay treatments for cancer but in some cases is not effective. Cancer stem cells (CSCs) within the tumor can be responsible for recurrence and metastasis after RT. Matrix metalloproteases (MMPs), regulated mainly b...

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Veröffentlicht in:Cancers 2019-11, Vol.11 (11), p.1781
Hauptverfasser: Olivares-Urbano, María Auxiliadora, Griñán-Lisón, Carmen, Ríos-Arrabal, Sandra, Artacho-Cordón, Francisco, Torralbo, Ana Isabel, López-Ruiz, Elena, Marchal, Juan Antonio, Núñez, María Isabel
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container_issue 11
container_start_page 1781
container_title Cancers
container_volume 11
creator Olivares-Urbano, María Auxiliadora
Griñán-Lisón, Carmen
Ríos-Arrabal, Sandra
Artacho-Cordón, Francisco
Torralbo, Ana Isabel
López-Ruiz, Elena
Marchal, Juan Antonio
Núñez, María Isabel
description Breast cancer is the most common cancer in women. Radiotherapy (RT) is one of the mainstay treatments for cancer but in some cases is not effective. Cancer stem cells (CSCs) within the tumor can be responsible for recurrence and metastasis after RT. Matrix metalloproteases (MMPs), regulated mainly by tissue inhibitors of metalloproteinases (TIMPs) and histone deacetylases (HDACs), may also contribute to tumor development by modifying its activity after RT. The aim of this work was to study the effects of RT on the expression of MMPs, TIMPs and HDACs on different cell subpopulations in MCF-7, MDA-MB-231 and SK-BR-3 cell lines. We assessed the in vitro expression of these genes in different 3D culture models and induced tumors in female NSG mice by orthotopic xenotransplants. Our results showed that gene expression is related to the cell subpopulation studied, the culture model used and the single radiation dose administered. Moreover, the crucial role played by the microenvironment in terms of cell interactions and CSC plasticity in tumor growth and RT outcome is also shown, supporting the use of higher doses (6 Gy) to achieve better control of tumor development.
doi_str_mv 10.3390/cancers11111781
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source PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central
subjects Angiogenesis
Apoptosis
Breast cancer
Cancer therapies
Cell culture
Cell cycle
Cell growth
Cell interactions
Enzymes
Gene expression
Histones
Medical prognosis
Metastases
Metastasis
Microenvironments
Phenotypes
Radiation
Radiation therapy
Stem cell transplantation
Stem cells
Tissue inhibitor of metalloproteinases
Tumors
Xenografts
title Radiation and Stemness Phenotype May Influence Individual Breast Cancer Outcomes: The Crucial Role of MMPs and Microenvironment
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