Exosomes from breast cancer cells stimulate proliferation and inhibit apoptosis of CD133+ cancer cells in vitro

Abstract

Exosomes are a family of bioactive vesicles that are secreted from various types of cell, including tumor cells. Exosomes derived from breast cancer cells have been demonstrated to perform important functions in tumor progression in vitro and in vivo. However, few studies exist regarding the function of exosomes in CD133+ breast cancer cells. In the present study, exosomes from 4T1 mouse breast cancer cells and mouse mammary gland epithelial cells were purified. The exosome-associated markers CD63, CD9 and CD81 were detected, and the size distribution and ζ potential of the exosomes were determined. Exosome uptake by CD133+ and CD133-4T1 cells was confirmed by confocal microscopy. An ATPlite assay indicated that the proliferation of CD133+ cells was increased and the apoptosis was suppressed by exosomes from 4T1 cells. Collectively, the findings of the present study demonstrate a novel mechanism by which the action of exosomes on CD133+ 4T1 cells may contribute to breast cancer progression.

The Role of Exosomes in Breast Cancer

“…For example, exosomes from 4T1 breast cancer cell mouse models were found to increase proliferation and suppress apoptosis of CD133 ϩ 4T1 cells, supporting the potential role of exosomes in tumor progression through evading apoptosis (35 ). Other studies, including human cells/clinical samples supporting a role for exosomes in evading apoptosis, are outlined below.…”

Exosome: emerging biomarker in breast cancer

“…MCF-7-derived exosomes up-regulated the activation marker CD44, the CSCs growth factor IL6, as well as ApoE. In another study, 4T1 mouse breast derived exosomes functioned as pro-tumorigenic factors by promoting the cell growth and suppression apoptosis of CD133 + tumor stem cells [75]. …”

Complex N‐glycan promotes CD133 mono‐ubiquitination and secretion

“…Extracellular membrane trafficking via exosomes and other plasma membrane-derived vesicles can promote tumor growth and metastasis [50]. Many studies have demonstrated that CD133-containing vesicles are involved in a series of important biological processes such as cell differentiation, cancer progression, and extracellular cell communication [15][16][17]. However, the underlying mechanisms of CD133 secretion remain largely unknown.…”

“…Transmission electron microscopy and sucrose density gradient fraction analysis showed that in addition to its localization in plasma membrane protrusions, CD133 is also found in EVs [14]. CD133-containing secretory vesicles are involved in biological processes such as cell differentiation [15], cancer progression [16], and extracellular cell communication [17]. Our previous study found that CD133-containing vesicles could be taken up by the recipient cells and promote recipient cells migration [14].…”