Pyroptosis of MCF7 Cells Induced by the Secreted Factors of hUCMSCs.

Bingrong Zheng,Luhan Yang,Zongliu Hou,Yang Jiao,Guodong Chen,Wei Si,Hongbo Zhao,Xiongbo Sang

doi:10.1155/2018/5912194

Bingrong Zheng, Luhan Yang + Show 6 more

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https://doi.org/10.1155/2018/5912194

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Abstract

Human umbilical cord mesenchymal stem cells (hUCMSCs) are superior to other sources of mesenchymal stem/stromal cells (MSCs), and they are used as a novel tool for cell-based cancer therapy. However, the mechanism underlying hUCMSC-induced cancer cell death is not clear. In the present study, we aimed to evaluate the effect of secreted factors of hUCMSCs on the breast cancer cell line MCF7 by exposing them to the conditioned medium (CM) of hUCMSCs. We evaluated the morphological changes, cell viability, cell cycle, apoptosis, DNA fragmentation, and interleukin-1β (IL-1β) secretion of CM-exposed MCF7 cells. The results showed that the secreted factors of hUCMSCs could cause MCF7 cell death by inducing pyroptosis. We also sequenced the total RNA, and the differentially expressed genes (DEGs) were subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A total of 2597 (1822 upregulated and 775 downregulated) genes were identified and 14 pathways were significantly enriched. The results showed that the expression of the pyroptosis-related genes NLRP1 and CASP4 and the inflammation-related pathways changed significantly in MCF7 cells exposed to the CM. To the best of our knowledge, this study is the first to report that the secreted factors of hUCMSCs can cause MCF7 cell pyroptosis. Furthermore, it is the first to examine the global gene expression in MCF7 cells exposed to CM. These results will provide valuable information for further studies on the mechanism of MCF7 cell pyroptosis induced by the secreted factors of hUCMSCs. It will also help understand the effect of hUCMSCs on cell-based breast cancer therapy.

Highlights

Breast cancer is the leading type of cancer among women, affecting approximately 2.1 million women [1] and resulting in 533,600 deaths in 2015 [2]
As secreted factors of hUCMCSs can inhibit cancer progression by inducing tumor cell death [12, 13], in the present study, we aimed to evaluate the effect of secreted factors of Human umbilical cord mesenchymal stem cells (hUCMSCs) on the breast cancer cell line MCF7, and we performed RNA-sequencing (RNA-Seq) to explore the genes and pathways involved in this process
We found that even 10% hUCMSC-cultured medium and 90% fresh medium can cause MCF7 cells pore-induced plasma membrane invagination and death

Summary

Introduction

Breast cancer is the leading type of cancer among women, affecting approximately 2.1 million women [1] and resulting in 533,600 deaths in 2015 [2]. In China, there has been an increase in the incidence of breast cancer, and it is expected to account for 15% of new cancer cases [3]. As breast cancers are classified by several grading systems, and as each of these can affect the prognosis and treatment response, a new effective treatment for breast cancer is necessary. Pyroptosis is a type of programmed cell death and is distinct from the immunologically silent apoptotic cell death, which is caspase-1 dependent [5]. The activity of caspase-1 can result in the maturation of IL-1β and IL-18 and cleave gasdermin D to induce pore opening and pyroptosis [6]. Inflammasomes are important for caspase-1 activity [7] and are composed of either AIM2-like receptor, tripartite motif-containing proteins, or the members of the

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