| Autor: |
Jiarong Li, Anne Camirand, Mahvash Zakikhani, Karine Sellin, Yubo Guo, XiaoRui Luan, Catalin Mihalcioiu, Richard Kremer |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
JBMR Plus, Vol 6, Iss 6, Pp n/a-n/a (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2473-4039 |
| DOI: |
10.1002/jbm4.10587 |
| Popis: |
ABSTRACT Parathyroid hormone‐related protein (PTHrP) plays a major role in skeletal metastasis but its action mechanism has not been fully defined. We previously demonstrated the crucial importance of PTHrP in promoting mammary tumor initiation, growth, and metastasis in a mouse model with a mammary epithelium‐targeted Pthlh gene ablation. We demonstrate here a novel mechanism for bone invasion involving PTHrP induction of epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs) regulation. Clustered regularly interspaced short palindromic repeats (CRISPR)‐mediated Pthlh gene ablation was used to study EMT markers, phenotype, and invasiveness in two triple‐negative breast cancer (TNBC) cell types (established MDA‐MB‐231 and patient‐derived PT‐TNBC cells). In vitro, Pthlh ablation in TNBC cells reduced EMT markers, mammosphere‐forming ability, and CD44high/CD24low cells ratio. In vivo, cells were injected intratibially into athymic nude mice, and therapeutic treatment with our anti‐PTHrP blocking antibody was started 2 weeks after skeletal tumors were established. In vivo, compared to control, lytic bone lesion from Pthlh ‐ablated cells decreased significantly over 2 weeks by 27% for MDA‐MB‐231 and by 75% for PT‐TNBC‐injected mice (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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