Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes
| Autor: | Sonja Thaler, Charles James Kirkpatrick, Erik Springer, Arno Schad, Marcus Schmidt, Jonathan P. Sleeman, Cristina Cotarelo |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Senescence Adult Pathology medicine.medical_specialty Receptor ErbB-2 Breast Neoplasms Triple Negative Breast Neoplasms Tumor initiation medicine.disease_cause Malignant transformation Metastasis 03 medical and health sciences 0302 clinical medicine Breast cancer medicine Biomarkers Tumor cellular senescence Humans Neoplasm Invasiveness Aged Cell Proliferation Neoplasm Staging Aged 80 and over Lamin Type B business.industry Oncogenes Middle Aged medicine.disease Immunohistochemistry breast cancer subtypes 030104 developmental biology Ki-67 Antigen Oncology Tumor progression 030220 oncology & carcinogenesis Mutation Cancer research Female Neoplasm Grading Tumor Suppressor Protein p53 Carcinogenesis business Research Paper breast cancer pathology |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Cristina L. Cotarelo 1 , Arno Schad 1 , Charles James Kirkpatrick 1 , Jonathan P. Sleeman 2, 3 , Erik Springer 1 , Marcus Schmidt 4 , Sonja Thaler 2 1 Institute of Pathology, University Medical Center, Johannes Gutenberg University, Mainz, Germany 2 Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany 3 KIT Campus Nord, Institute for Toxicology and Genetics, Karlsruhe, Germany 4 Department of Obstetrics and Gynecology, University Medical Center, Johannes Gutenberg University, Mainz, Germany Correspondence to: Sonja Thaler, email: Sonja.Thaler@medma.uni-heidelberg.de , Sonja.Thaler@gmx.de Keywords: cellular senescence, breast cancer subtypes, breast cancer pathology Received: December 23, 2015 Accepted: September 12, 2016 Published: October 04, 2016 ABSTRACT Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program. Breast cancer represents a heterogenous disease that can be divided into breast cancer subtypes due to different subsets of genetic and epigenetic abnormalities. As tumor initiation and progression of these breast cancer subtypes is triggered by diverse oncogenic stimuli, differences in the senescence secretomes within breast tumors might be responsible for tumor initiation, progression, metastasis and therapeutic response. Many studies have addressed the role of senescence as a barrier to tumor progression using murine xenograft models. However, few investigations have been performed to elucidate the degree to which senescent tumor cells are present within untreated human tumors, and if present, whether these senescent tumor cells may play a role in disease progression. In the present study we analysed the appearance of senescent cells within invasive breast cancers. Detection of cellular senescence by the use of SAβ-galactosidase (SAβ-gal) staining within invasive breast carcinoms from 129 untreated patients revealed differences in the amount of SAβ-gal+ tumor cells between breast cancer subtypes. The highest percentages of SAβ-gal+ tumor cells were found in HER2-positive and luminal A breast carcinomas whereas triple negative tumors showed either little or no positivity. |
| Databáze: | OpenAIRE |
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