Tumor cell-secreted exosomal miR-22-3p inhibits transgelin and induces vascular abnormalization to promote tumor budding.
Mol Ther
; 29(6): 2151-2166, 2021 06 02.
Article
in En
| MEDLINE
| ID: mdl-33578038
ABSTRACT
Tumor budding (TB) is considered a histomorphological marker of poor prognosis in patients with breast cancer (BC). Tumor vasculature is disordered and unstable in BC, which causes restricted drug delivery, hypoxia, and tumor metastasis. Traditional anti-angiogenic treatments cause extreme hypoxia, increased invasion, metastasis, and drug resistance due to blood vessel rarefaction or regression. Therefore, the application of anti-angiogenic strategies for vascular normalization in tumors is crucial to improve therapeutic efficacy in BC. In the present study, we found that transgelin (TAGLN) promoted the normalization of tumor vessels by regulating the structure and function of endothelial cells, and knockout of TAGLN in tumor-bearing mice resulted in tumor vessel abnormalization, an increase in epithelial-mesenchymal transition characteristics of tumor cells, and promotion of TB. Moreover, BC cells secrete exosomal miR-22-3p that mediates tumor vessel abnormalization by inhibiting TAGLN. We demonstrated for the first time that TAGLN plays an essential role in tumor vessel normalization, and thus it impairs TB and metastasis. Additionally, the findings of this study indicate that exosomal miR-22-3p is a potential therapeutic target for BC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Neoplastic
/
MicroRNAs
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RNA Interference
/
Exosomes
/
Microfilament Proteins
/
Muscle Proteins
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Neovascularization, Pathologic
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Mol Ther
Journal subject:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Year:
2021
Document type:
Article