Extracellular Acidosis Stimulates Breast Cancer Cell Motility Through ...

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Abstract

A reduction in extracellular pH (pHe) is a characteristic of most malignant tumors. The aryl hydrocarbon receptor (AhR) is a transcription factor localized in a cytosolic complex with c-Src, which allows it to trigger nongenomic effects through c-Src. Considering that the slightly acidic tumor microenvironment promotes breast cancer progression in a similar way to the AhR/c-Src axis, our aim was to evaluate whether this pathway could be activated by low pHe. We examined the effect of pHe 6.5 on AhR/c-Src axis using two breast cancer cell lines (MDA-MB-231 and LM3) and mammary epithelial cells (NMuMG) and found that acidosis increased c-Src phosphorylation only in tumor cells. Moreover, the presence of AhR inhibitors prevented c-Src activation. Low pHe reduced intracellular pH (pHi), while amiloride treatment, which is known to reduce pHi, induced c-Src phosphorylation through AhR. Analyses were conducted on cell migration and metalloproteases (MMP)-2 and -9 activities, with results showing an acidosis-induced increase in MDA-MB-231 and LM3 cell migration and MMP-9 activity, but no changes in NMuMG cells. Moreover, all these effects were blocked by AhR and c-Src inhibitors. In conclusion, acidosis stimulates the AhR/c-Src axis only in breast cancer cells, increasing cell migration and MMP-9 activity. Although the AhR activation mechanism still remains elusive, a reduction in pHi may be thought to be involved. These findings suggest a critical role for the AhR/c-Src axis in breast tumor progression stimulated by an acidic microenvironment.

Keywords: aryl hydrocarbon receptor; breast cancer; c-Src; low pH; metalloprotease; migration.

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References

REFERENCES

    1. Riemann A, Schneider B, Gundel D, Stock C, Gekle M, Thews O. Acidosis promotes metastasis formation by enhancing tumor cell motility. Adv Exp Med Biol. 2016;876:215-220. doi:10.1007/978-1-4939-3023-4_27
    1. Putnam RW. Intracellular pH regulation. In: Sperelakis N., ed. Cell physiology sourcebook. 4th ed. Academic Press; 2012:357-372.
    1. Gatenby RA, Gawlinski ET, Gmitro AF, Kaylor B, Gillies RJ. Acid-mediated tumor invasion: a multidisciplinary study. Cancer Res. 2006;66:5216-5223. doi:10.1158/0008-5472.CAN-05-4193
    1. Koltai T. Cancer: fundamentals behind pH targeting and the double-edged approach. Onco Targets Ther. 2016;9:6343-6360. doi:10.2147/OTT.S115438
    1. Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011;11:671-677. doi:10.1038/nrc3110
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  • Acidosis* Actions
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  • Breast Neoplasms* / metabolism Actions
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  • Receptors, Aryl Hydrocarbon Actions
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Grants and funding

  • PICT 2016/Agencia Nacional de Promoción Científica y Tecnológica
  • Nro 2054/Agencia Nacional de Promoción Científica y Tecnológica
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  • PID 20020130100631BA/Universidad de Buenos Aires
  • PIP0654/Consejo Nacional de Investigaciones Científicas y Técnicas
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