Decreased differentiation capacity and altered expression of extracellular matrix components in irradiation-mediated senescent human breast adipose-derived stem cells.
Adipose Tissue
/ metabolism
Cell Differentiation
/ physiology
Cells, Cultured
Collagen Type I
Core Binding Factor Alpha 1 Subunit
/ metabolism
Decorin
/ metabolism
Extracellular Matrix
/ genetics
Humans
Intercellular Adhesion Molecule-1
/ metabolism
Interleukin-6
/ metabolism
Interleukin-8
/ metabolism
Matrix Metalloproteinase 1
/ metabolism
Matrix Metalloproteinase 13
/ metabolism
PPAR gamma
/ metabolism
Stem Cells
/ metabolism
Syndecan-1
/ metabolism
Syndecan-4
/ metabolism
MMPs
adipose-derived stem cells
breast stroma
collagen
decorin
interleukins
ionizing irradiation
proteoglycans
senescence
syndecan
Journal
IUBMB life
ISSN: 1521-6551
Titre abrégé: IUBMB Life
Pays: England
ID NLM: 100888706
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
28
02
2022
accepted:
06
06
2022
pubmed:
15
7
2022
medline:
21
9
2022
entrez:
14
7
2022
Statut:
ppublish
Résumé
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 prognostic factors for tumor development. In conclusion, we showed that ionizing radiation-mediated prematurely senescent human breast ASCs have a decreased differentiation potential and express specific changes adding to the formation of a permissive environment for tumor growth.
Substances chimiques
Collagen Type I
0
Core Binding Factor Alpha 1 Subunit
0
Decorin
0
Interleukin-6
0
Interleukin-8
0
PPAR gamma
0
Syndecan-1
0
Syndecan-4
0
Intercellular Adhesion Molecule-1
126547-89-5
Matrix Metalloproteinase 13
EC 3.4.24.-
Matrix Metalloproteinase 1
EC 3.4.24.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
969-981Informations de copyright
© 2022 International Union of Biochemistry and Molecular Biology.
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