Decreased differentiation capacity and altered expression of extracellular matrix components in irradiation‐mediated senescent human breast adipose‐derived stem cells

Abstract

Radiotherapy is widely used for the treatment of breast cancer. However, we have shown that ionizing radiation can provoke premature senescence in breast stromal cells. In particular, breast stromal fibroblasts can become senescent after irradiation both in vitro and in vivo and they express an inflammatory phenotype and an altered profile of extracellular matrix components, thus facilitating tumor progression. Adipose-derived stem cells (ASCs) represent another major component of the breast tissue stroma. They are multipotent cells and due to their ability to differentiate in multiple cell lineages they play an important role in tissue maintenance and repair in normal and pathologic conditions. Here, we investigated the characteristics of human breast ASCs that became senescent prematurely after their exposure to ionizing radiation. We found decreased expression levels of the specific mesenchymal cell surface markers CD105, CD73, CD44, and CD90. In parallel, we demonstrated a significantly reduced expression of transcription factors regulating osteogenic (i.e., RUNX2), adipogenic (i.e., PPARγ), and chondrogenic (i.e., SOX9) differentiation; this was followed by an analogous reduction in their differentiation capacity. Furthermore, they overexpress inflammatory markers, that is, IL-6, IL-8, and ICAM-1, and a catabolic phenotype, marked by the reduction of collagen type I and the increase of MMP-1 and MMP-13 expression. Finally, we detected changes in proteoglycan expression, for example, the upregulation of syndecan 1 and syndecan 4 and the downregulation of decorin. Notably, all these alterations, when observed in the breast stroma, represent poor

Lipid Regulatory Element Interact with CD44 on Mitochondrial Bioenergetics in Bovine Adipocyte Differentiation and Lipometabolism

“…Moreover, numerous investigations have demonstrated that CD44 is a cell surface marker of preadipocytes and mesenchymal stem cells. − We speculate that CD44 also plays an equally important role in the differentiation of mesenchymal stem cells into preadipocytes during the entire process of cell differentiation. In light of the abovementioned findings, it is still quite exciting to speculate about the hidden molecular processes by which CD44 controls lipid metabolism.…”

CD44 and its implication in neoplastic diseases

“…For instance, the overexpression of CD44 was reported to reduce the levels of MMPs for the maintenance of ECM homeostasis 174 . In Papadopoulou's study, 175 the increase in MMP1 and MMP13 expression followed by the decreased expression levels of CD44 was found to promote tumor growth. Another study also showed that MMP2 activation contributed to decrease the number of CD44 + /CD24 − cells in MDA‐MB‐231 cells after normothermic microwave treatment 176 .…”

Mesenchymal Stem Cell Transplantation Has a Regenerative Effect in Ischemic Myocardium: An Experimental Rat Model Evaluated by SPECT-CT Assessment

“…Novel DNA synthesis was performed with dual labeling with 5-bromo-2 ′ -deoxyuridine (BrdU) and 4 ′ ,6-diamino-2-phenylindole (DAPI) dihydrochloride (Sigma, Kawasaki City, Japan) [1][2][3]. Furthermore, ADSCs' cell surface markers were examined, as described before [27].…”