Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes
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Cristina L. Cotarelo1, Arno Schad1, Charles James Kirkpatrick1, Jonathan P. Sleeman2,3, Erik Springer1, Marcus Schmidt4, Sonja Thaler2
1Institute of Pathology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
2Centre for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
3KIT Campus Nord, Institute for Toxicology and Genetics, Karlsruhe, Germany
4Department of Obstetrics and Gynecology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
Sonja Thaler, email: [email protected], [email protected]
Keywords: cellular senescence, breast cancer subtypes, breast cancer pathology
Received: December 23, 2015 Accepted: September 12, 2016 Published: October 04, 2016
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.
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