Acidic microenvironment induction of interleukin-8 expression and matrix metalloproteinase-2/-9 activation via acid-sensing ion channel 1 promotes breast cancer cell progression
| Autor: | Haruka Yamakawa, Naoko Kawabe, Ayaka Korechika, Yasuteru Muragaki, Kazuma Nakai, Masako Nakanishi |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Cell Breast Neoplasms Matrix metalloproteinase Metastasis Cell Movement Cell Line Tumor medicine Tumor Microenvironment Humans Interleukin 8 Phosphorylation Receptor Chemistry Interleukin-8 Transcription Factor RelA Cancer Interleukin Cell migration General Medicine Hydrogen-Ion Concentration medicine.disease Culture Media Acid Sensing Ion Channels Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Matrix Metalloproteinase 9 Cancer research Matrix Metalloproteinase 2 Female |
| Zdroj: | Oncology reports. 45(3) |
| ISSN: | 1791-2431 |
| Popis: | The cancer microenvironment exhibits local acidosis compared with the surrounding normal tissue. Many reports have shown that acidosis accelerates the invasiveness and metastasis of cancer, yet the underlying molecular mechanisms remain unclear. In the present study, we focused on acid-induced functional changes through acid receptors in breast cancer cells. Acidic treatment induced interleukin (IL)-8 expression in MDA-MB-231 cells and promoted cell migration and invasion. The acidic microenvironment elevated matrix metalloproteinase (MMP)-2 and MMP-9 activity, and addition of IL-8 had similar effects. However, inhibition of IL-8 suppressed the acid-induced migration and invasion of MDA-MB-231 cells. MDA-MB-231 cells express various acid receptors including ion channels and G protein-coupled receptors. Interestingly, acidic stimulation increased the expression of acid-sensing ion channel 1 (ASIC1), and acid-induced IL-8 was significantly decreased by ASIC1 knockdown. Moreover, phosphorylation of nuclear factor (NF)-κB was induced by acidic treatment, and inhibition of NF-κB activation reduced acid-induced IL-8 expression. These results suggest that IL-8 induction by an acidic microenvironment promotes breast cancer development and that ASIC1 might be a novel therapeutic target for breast cancer metastasis. |
| Databáze: | OpenAIRE |
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