Cellular Senescence in Normal Mammary Gland and Breast Cancer. Implications for Cancer Therapy
Chaido Sirinian, Stavros Peroukidis, Katharina Kriegsmann, Dimitrios Chaniotis, Αngelos Koutras, Mark Kriegsmann, Anastasios D. Papanastasiou
Abstract
Cellular senescence (CS) is a major homeostatic biological process, which plays a key role in normal tissue development and provides protection from stressful cell insults. The role of CS in mammary-gland development and breast cancer is not well understood. While there is a lack of experimental data on the role of CS in the development of the pre-pubertal mammary gland, there is evidence for a biphasic senescence response in adult normal-mammary-epithelial cells, where the bypass of the first senescence barrier (M0) seems to be a key step in the development of premalignant lesions, with genetic abnormalities that resemble in situ breast carcinoma. Further, there is accumulating evidence for the role of cellular senescence in breast-cancer response, regarding treatment and patient outcome. Here, we review the current literature on cellular senescence, in epithelial-mammary cells, breast-cancer cells, and breast-tumor-microenvironment-resident cells. Furthermore, we discuss its putative role in breast-cancer response, regarding treatment and disease progression. In addition, we provide preliminary evidence of CS in breast-cancer-microenvironment cells, such as tumor-associated fibroblasts and tumor-infiltrating lymphocytes, by employing the novel GL13 lipofuscin stain, as a marker of cellular senescence.