The role of acidic microenvironment in the tumor aggressive phenotypes and the treatment
Journal Title: Traditional Medicine Research - Year 2020, Vol 5, Issue 1
Abstract
Recently, the scammer who advocated "acid constitution" as the source of all diseases was fined 105 million US dollars, and the "acid-base balance" theory he founded was also criticized. Although the "acid constitution" of the human body is full of pseudoscience, many tumors are indeed "acid constitution". Increased glycolysis, hypoxia, and insufficient tissue perfusion as well as a large amount of acid and metabolite metabolites that accumulated in the tumor microenvironment, making the tumor microenvironment acidic [1–3]. Microenvironment acidification plays an important role in tumor progression and can provide a favorable environment for tumor cell generation [4]. Acidosis is one of the basic characteristics of tumor microenvironment. Unlike normal cells, cancer cells can adapt to a low pH environment by increasing glycolysis, while activating the activity and expression of proton transporters that normalize the pH in the cell [1–4]. Acidosis-driven adaptation also triggers the emergence of aggressive tumor cells in subpopulations that exhibit increased invasion, proliferation, and resistance [5]. Acidosis can also promote immune escape and thus maintain tumor growth [6, 7]. Although there is an important relationship between too much lactic acid in tumor microenvironment and tumor cell invasion, few studies have explored which areas in the tumor are acidic and how too much lactate affects gene expression to promote tumor invasion. Researchers have conducted in-depth research on this issue and found that the slightly acidic environment in tumors can help cancer cells produce proteins that make them more malignant. Related research results have been published in Cancer Research [8]. Researchers determined the acidic sites in tumors by injecting a tumor-tagged mouse with a fluorescently labeled pH-responsive polypeptide. Unexpectedly, the researchers found that the acidic region not only overlapped with the hypoxic region, but also with the highly proliferative and highly invasive cell regions at the tumor matrix interface. These regions were characterized by increased expression of matrix metalloproteinase and degradation of the basement membrane degree. By performing RNA sequencing of cells in the low pH region, the researchers found that the reset of the transcriptome involved in RNA splicing increased the targets of RNA-binding proteins that specifically bind to AU-rich sequences. The low-pH signature indicated extensive changes in alternative splicing and was notably enriched for splicing of genes implicated in regulation of adhesion and cell migration. Surprisingly, this selective shear could be reversed by experiments that neutralize the acidic environment in vitro and in vivo. These findings reveal the impact of local acidity in tumor microenvironment on tumor invasion and metastasis.
Authors and Affiliations
Jian Hao
Keywords
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- EP ID EP675807
- DOI 10.12032/TMR20191231153
- Views 262
- Downloads 0
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