Effects of metformin on human bone-derived mesenchymal stromal cell-breast cancer cell line interactions.
Adipokines
Bone-derived mesenchymal stromal cells
Breast cancer
Metformin
Migration assay
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
12 Feb 2022
12 Feb 2022
Historique:
received:
15
12
2021
accepted:
10
01
2022
entrez:
12
2
2022
pubmed:
13
2
2022
medline:
22
3
2022
Statut:
epublish
Résumé
Metformin is used to treat patients with type 2 diabetes mellitus and was found to lower the incidence of cancer. Bone metastasis is a common impairment associated with advanced breast cancer. The present study investigated the effects of metformin on human bone-derived mesenchymal stromal cells (BM-MSC)-breast cancer cell line interactions. BM-MSCs grown from box chisels were tested for growth-stimulating and migration-controlling activity on four breast cancer cell lines either untreated or after pretreatment with metformin. Growth stimulation was tested in MTT tests and migration in scratch assays. Furthermore, the expression of adipokines of BM-MSCs in response to metformin was assessed using Western blot arrays. Compared to breast cancer cell lines (3.6 ± 1.4% reduction of proliferation), 500 µM metformin significantly inhibited the proliferation of BM-MSC lines (mean 12.3 ± 2.2 reduction). Pretreatment of BM-MSCs with metformin showed variable effects of the resulting conditioned media (CM) on breast cancer cell lines depending on the specific BM-MSC-cancer line combination. Metformin significantly reduced the migration of breast cancer cell lines MDA-MB-231 and MDA-MB-436 in response to CM of drug-pretreated BM-MSCs. Assessment of metformin-induced alterations in the expression of adipokines by BM-MSC CM indicated increased osteogenic signaling and possibly impairment of metastasis. In conclusion, the anticancer activities of metformin are the result of a range of direct and indirect mechanisms that lower tumor proliferation and progression. A lower metformin-induced protumor activity of BM-MSCs in the bone microenvironment seem to contribute to the positive effects of the drug in selected breast cancer patients.
Identifiants
pubmed: 35150338
doi: 10.1007/s12032-022-01655-6
pii: 10.1007/s12032-022-01655-6
pmc: PMC8840908
doi:
Substances chimiques
Adipokines
0
Culture Media, Conditioned
0
Metformin
9100L32L2N
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
54Subventions
Organisme : Hochschuljubiläumsstiftung der Stadt Wien
ID : 19090
Informations de copyright
© 2022. The Author(s).
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