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Global transcriptomic alterations in MDA-MB-231 cells following high salt treatment

ABSTRACT: Difference in salt concentration may cause dramatic alterations in tumor microenvironment, progression of cancer and overall outcome of cancer therapy. Immune cells in tumor microenvironment are mostly immunosuppressed under the influence of tumor cells. Recent studies has shown that high salt induces immune cells to pro-inflammatory state in the tumor microenvironment. On contrary, it hinders the immunosuppressive functions of regulatory T cells, which plays an important role in inhibiting anti-cancer immune responses in tumor microenvironment. Salt- mediated induction of the immune cells to pro-inflammatory state could potentially enhance their transition from the immunosuppressed state to their innate pro- inflammatory state, thereby facilitating their effectiveness in combating the tumor and suppressing tumor progression. The role of high salt in cancer is controversial with only a few studies suggesting the potential pro-tumorigenic effect of high salt. Dietary salt increased the risk of gastric cancer, contributing to both the incidence and mortality of the disease by damaging the gastric mucosal lining. Another research indicated that a high salt diet could stimulate the growth of breast cancer and promote lung metastasis by elevating Th17 cell levels. In contrast, high salt containing diets significantly inhibited tumor growth, primarily through the depletion and functional modulation of myeloid-derived suppressor cells (MDSCs), highlighting its anti-cancer efficacy. High salt reduced cytokine production necessary for the expansion of myeloid-derived suppressor cells (MDSCs) and decreases MDSC accumulation in blood, spleen, and tumors. High salt diet in mice also showed increased Bifidobacterium abundance and heightened gut permeability, leading to intratumor localization of Bifidobacterium and enhancing NK cell functions. This facilitated tumor regression, suggesting potential role of high salt in cancer immunotherapy. The overall impact of high-salt diets is not fully understood, which necessitates further research to elucidate their influence in altering tumor microenvironment and fate of cancer cells. This study aimed to investigate the effects of high salt on a triple-negative breast cancer cell line (in vitro), exploring its impact on cancer progression and associated global transcriptomic changes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE265934 | GEO | 2024/10/30

REPOSITORIES: GEO

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Project description:Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that accumulate in the tumor microenvironment of most cancer patients. There MDSCs suppress both adaptive and innate immune responses, hindering immunotherapies. Moreover, many cancers are accompanied by inflammation, a processes that further intensifies MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSCs collected from tumor-bearing mice profusely release nano-scale membrane-bound extracellular vesicles, called exosomes, which carry biologically active proteins between cells and contribute directly to the immune suppressive functions of MDSC. Many studies on other cell types have shown that exosomes may also carry microRNAs (miRNAs) and messenger RNAs (mRNAs) which can also be transferred to surrounding and distant cells. However, to the best of our knowledge, the miRNA and mRNA cargo of MDSC-derived exosomes has not yet been interrogated. This study aims to identify and quantify the cargo of MDSC and their immunosuppressive exosomes to gather knowledge that can offer insights on the mechanisms by which MDSCs contribute to immune suppression, focusing on the role of exosomes as intercellular communication mediators in the tumor microenvironment. In order to achieve our objective a well-established mouse model based on a conventional mammary carcinoma (4T1 cells) and heightened inflammation (4T1 transduced to express the cytokine interleukin-1b) was used. We provide evidence that MDSC-derived exosomes carry proteins, mRNAs and miRNAs. Relative quantitation demonstrated quantitative differences between the exosome cargo and the cargo of their parental cells, supporting the hypothesis that selective loading into the exosomes is possible. Additionally, quantitative and functional analyses of the exosome cargo generated under conventional and heightened inflammation conditions are consistent with clinical observations that inflammation is linked to cancer development.

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Global transcriptomic alterations in MDA-MB-231 cells following high salt treatment

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