PUBLICATION
Small Extracellular Vesicles Deliver TGF-β1 and Promote Adriamycin Resistance in Breast Cancer Cells
- Authors
- Tan, C., Sun, W., Xu, Z., Zhu, S., Hu, W., Wang, X., Zhang, Y., Zhang, G., Wang, Z., Xu, Y., Tang, J.
- ID
- ZDB-PUB-210129-17
- Date
- 2021
- Source
- Molecular Oncology 15(5): 1528-1542 (Journal)
- Registered Authors
- Keywords
- EMT, TGF-β1, adriamycin resistance and breast cancer, apoptosis, sEVs
- MeSH Terms
-
- Animals
- Antibiotics, Antineoplastic/therapeutic use
- Apoptosis/drug effects
- Apoptosis/genetics
- Breast Neoplasms/drug therapy*
- Breast Neoplasms/genetics
- Breast Neoplasms/pathology
- Doxorubicin/therapeutic use*
- Drug Resistance, Neoplasm*/genetics
- Embryo, Nonmammalian
- Extracellular Vesicles/metabolism*
- Extracellular Vesicles/physiology
- Female
- Humans
- MCF-7 Cells
- Paracrine Communication/genetics
- Transforming Growth Factor beta1/genetics
- Transforming Growth Factor beta1/metabolism*
- Tumor Microenvironment/genetics
- Zebrafish/embryology
- PubMed
- 33508878 Full text @ Mol. Oncol.
Citation
Tan, C., Sun, W., Xu, Z., Zhu, S., Hu, W., Wang, X., Zhang, Y., Zhang, G., Wang, Z., Xu, Y., Tang, J. (2021) Small Extracellular Vesicles Deliver TGF-β1 and Promote Adriamycin Resistance in Breast Cancer Cells. Molecular Oncology. 15(5):1528-1542.
Abstract
Chemotherapeutic resistance is a major obstacle in the control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we describe that sEVs-mediated TGF-β1 intercellular transfer is involved in the drug-resistant transmission. sEVs were isolated and characterized from both sensitive and resistant cells. sEVs derived from the resistant cells were incubated with the sensitive cells and resulted in transmitting the resistant phenotype to the recipient cells. Cytokine antibody microarray revealed that most metastasis-associated cytokines present at the high levels in sEVs from the resistant cells compared to their levels in sEVs from the sensitive cells, particularly, TGF-β1 is enriched in sEVs from the resistant cells. The sEVs-mediated TGF-β1 intercellular transfer led to increasing Smad2 phosphorylation and improving cell survival by suppressing apoptosis and enhancing cell mobility. Furthermore, sEVs-mediated drug-resistant transmission by delivering TGF-β1 was validated using a zebrafish xenograft tumor model. These results elaborated that sEVs-mediated TGF-β1 intercellular transfer contributes to adriamycin resistance in BCa.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping