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Fig. 5 | Journal of Nanobiotechnology

Fig. 5

From: Core–shell nanoparticles suppress metastasis and modify the tumour-supportive activity of cancer-associated fibroblasts

Fig. 5

AgNP and Au@Ag treatments induce similar transcriptomic changes in CAFs. In order to reveal potential mechanisms in the background of the tumour modulatory effects of CAFs, NIH/3T3 fibroblasts—co-cultured with 4T1 tumour cells—were treated with nanoparticles then transcriptome analysis was performed. Heat map showing the observed gene expressional changes indicates that AgNP and Au@Ag nanoparticle treatments induced similar transcriptomic profiles, with significant transcriptomic alterations in several hundred genes (a). Gene ontology analysis of repressed and induced genes as well as of upregulated pathways was performed to link the observed transcriptomic changes to biological functions. Both AgNP and Au@Ag nanoparticles repressed the transcription of cell cycle- and cell division-related genes, however, only AgNPs induced cell death-associated gene expressional changes (b). Among the repressed and upregulated genes, several genes have secreted protein products which are related to cancer metastasis. AgNP and Au@Ag nanoparticle treatments decreased the majority of these metastasis-related genes in cancer associated fibroblasts (c). Kaplan–Meier plot of breast cancer patients with low and high Spp1 expression indicates that the elevated expression of Spp1 significantly worsens the survival of patients highlighting the clinical significance of intratumoural Osteopontin levels (d). TCGA patient data indicates that Spp1 expression is upregulated in breast cancer (e). Elevated Spp1 expression is associated to metastasis in 4T1 tumour model (f). Au@Ag treatments do not influence the expression levels of CAF markers alphaSMA and Vimentin, while significantly reduce intratumoural Osteopontin expression in vivo (g, h). Full-length blots are presented as Additional file 18

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