Cancer-Associated Exosomal CBFB Facilitates the Aggressive Phenotype, Evasion of Oxidative Stress, and Preferential Predisposition to Bone Prometastatic Factor of Breast Cancer Progression

Figure 3

Exosomes rich in CBFB promoted the generation of CAF-like phenotype. (a) HMF3A cells treated with CBFB-rich exosome derived from bone metastatic patients with breast cancer (exosomes) exhibited significant increases in CAF markers, including vimentin (Vim), FAP, and α-SAM, and decreases in cytokeratin (KRT1) in immortalized human mammary fibroblast cell line HMF3A. (b) The CAF-like (VIM+/αSMA+) cell percentages increased following the exosomes treatment. (c) The Western blot results demonstrated CBFB upregulation in the HMF3A cells treated with exosomes. HMF3A-exosomes cocultured with low-metastatic-potential breast cancer cell lines exhibited enhanced metastatic potential. Both low-metastatic-potential breast cancer cell lines, MCF12A and T47D, exhibited enhanced migration (d) and invasion (e) abilities compared with their control counterparts. Representative images of invasion are shown. Scale bars: 200 μm. (f) ELISA analyses of exosome-induced CAFs. CAFs generated from exosome coculture demonstrated an increased secretion of IL-6 and OPN into the culture medium. , .

(a)

(b)

(c)

(d)

(e)

(f)