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Core-shell nanoparticles suppress metastasis and modify the tumour-supportive activity of cancer-associated fibroblasts.
- Source :
-
Journal of nanobiotechnology [J Nanobiotechnology] 2020 Jan 21; Vol. 18 (1), pp. 18. Date of Electronic Publication: 2020 Jan 21. - Publication Year :
- 2020
-
Abstract
- Background: Although accumulating evidence suggests that the crosstalk between malignant cells and cancer-associated fibroblasts (CAFs) actively contributes to tumour growth and metastatic dissemination, therapeutic strategies targeting tumour stroma are still not common in the clinical practice. Metal-based nanomaterials have been shown to exert excellent cytotoxic and anti-cancerous activities, however, their effects on the reactive stroma have never been investigated in details. Thus, using feasible in vitro and in vivo systems to model tumour microenvironment, we tested whether the presence of gold, silver or gold-core silver-shell nanoparticles exerts anti-tumour and metastasis suppressing activities by influencing the tumour-supporting activity of stromal fibroblasts.<br />Results: We found that the presence of gold-core silver-shell hybrid nanomaterials in the tumour microenvironment attenuated the tumour cell-promoting behaviour of CAFs, and this phenomenon led to a prominent attenuation of metastatic dissemination in vivo as well. Mechanistically, transcriptome analysis on tumour-promoting CAFs revealed that silver-based nanomaterials trigger expressional changes in genes related to cancer invasion and tumour metastasis.<br />Conclusions: Here we report that metal nanoparticles can influence the cancer-promoting activity of tumour stroma by affecting the gene expressional and secretory profiles of stromal fibroblasts and thereby altering their intrinsic crosstalk with malignant cells. This potential of metal nanomaterials should be exploited in multimodal treatment approaches and translated into improved therapeutic outcomes.
- Subjects :
- Alloys chemistry
Animals
Antineoplastic Agents therapeutic use
Cancer-Associated Fibroblasts pathology
Cell Line, Tumor
Cell Movement
Cell Survival
Disease Progression
Doxorubicin chemistry
Doxorubicin therapeutic use
Female
Fibroblasts cytology
Fibroblasts drug effects
Gene Expression Regulation, Neoplastic
Gold chemistry
Humans
Metal Nanoparticles therapeutic use
Mice, Inbred BALB C
Neoplasm Metastasis pathology
Neoplasm Transplantation
Silver chemistry
Tumor Microenvironment drug effects
Antineoplastic Agents chemistry
Cancer-Associated Fibroblasts drug effects
Metal Nanoparticles chemistry
Neoplasm Metastasis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1477-3155
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of nanobiotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 31964403
- Full Text :
- https://doi.org/10.1186/s12951-020-0576-x