Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis

Abstract

Exosomes have recently become the subject of increasing research interest. Interactions between tumor and host cells via exosomes play crucial roles in the initiation, progression and invasiveness of breast cancer. In our study, we used exosomes isolated from a co-culture model of THP-1-derived macrophages exposed to apoptotic MCF-7 or MDA-MB-231 breast cancer cell line cells to investigate their effects on naïve MCF-7 or MDA-MB-231 cells in vitro and in vivo. This post-chemotherapy tumor microenvironment model allowed us to explore possible mechanisms that explain increased proliferation and metastasis of breast cancer seen in some patients. Our results suggest that while exosomes derived from macrophages normally inhibit proliferation and metastasis of MCF-7 or MDA-MB-231 cells, exposure of macrophages to breast cancer cells that have experienced chemotherapy are modified them to promote these processes. Exosomes from macrophages exposed to apoptotic cancer cells have increased amounts of IL-6 that increases the phosphorylation of STAT3, which likely explains the increased transcription of STAT3 target genes such as CyclinD1, MMP2 and MMP9. These observations suggest that the inhibition of exosome secretion and STAT3 signaling pathway activation might suppress the growth and metastasis of malignant tumors, and provide new targets for therapeutic treatment of malignant tumors after chemotherapy.

RETRACTED: Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2

“…Hence, it's a necessity to further investigate the underlying mechanism in LUAD progression, and seek for novel biomarkers for targeted diagnosis and therapy. Recently, exosomes have been deeply researched, and increasing evidence has suggested that exosomes play important roles in cell communication, tumorigenesis, tumor metastasis and microenvironment (Feng et al, 2019;Samuel and Gabrielsson, 2019;Yu et al, 2019). Notably, exosomes can function on tumor progression through releasing miRNAs to receptors in an internalization manner, and exosomes derived from diverse cells work different (De Feo et al, 2019;Kulkarni et al, 2019;Liu et al, 2019).…”

Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression

“…Studies have suggested that macrophage-derived exosomes can inhibit metastasis of ovarian tumor cells or cause fibrosarcoma regression [18,19]. Others reported that exosomes secreted by a macrophage cell line supported aggressiveness of pancreatic ductal adenocarcinoma as well as breast and gastric cancers [20][21][22]. None of these earlier studies considered a possibility that GBex-reprogrammed macrophages secreted exosomes which contributed to establishing the pro-tumor milieu.…”

Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

“…Tumor progression was augmented by exosomal miRNAs from TP53-mutant cells in colon cancer cells [ 98 ] and by exosomal lncRNA ZFAS1 in GC [ 92 ]. Exosomal miR-21 reduced apoptosis in GC cells [ 99 ], exosomal IL-6 induced metastasis in BC cells [ 100 ], exosomal HSP70 induced tumor progression in MSC cells [ 101 ], and exosomal TGF-β promoted tumor growth in LAMA84 cells [ 102 ]. Various recent studies based on the tumor promoting effect of exosomes have been listed in Table 2 .…”