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Local strong acids: A driving force for metastasis.

Yulin Wan1, Xiaoqian Ma2, Yin Li1

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Local acid buildup, particularly hydrogen chloride, may drive cancer metastasis. Bicarbonate and weak organic acids show anticancer effects by altering tumor pH and attracting chloride, suggesting a new therapeutic avenue.

Keywords:
Basic amino acid contentCCDC25Hydrogen chlorideMetastasisNeutrophil extracellular traps

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Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Carcinogenesis is potentially linked to local accumulation of strong acids like hydrogen chloride, which may promote metastasis.
  • Previous research indicated that bicarbonate can increase tumor pH and inhibit metastasis.
  • Neutrophil extracellular traps (NETs) contain DNA with phosphate groups capable of accepting protons and proteins with high basic amino acid content that attract anions.

Purpose of the Study:

  • To investigate the role of local acid buildup in cancer metastasis.
  • To explore the potential of targeting tumor acidity for cancer therapy.
  • To understand the interaction between neutrophil extracellular traps and acidic microenvironments.

Main Methods:

  • Analysis of the chemical properties of neutrophil extracellular traps components.
  • Assessment of the proton-accepting and anion-attracting capacities of NETs.
  • Review of existing studies on bicarbonate and weak organic acids in cancer treatment.

Main Results:

  • Neutrophil extracellular traps possess components that can attract anions like chloride, driven by basic amino acid content.
  • The protein CCDC25 in NETs exhibits a high basic amino acid content (20.2%), comparable to oncoproteins.
  • Local hydrogen chloride is proposed as a key factor in metastasis, and weak organic acids demonstrate anticancer effects.

Conclusions:

  • Local hydrogen chloride accumulation may be a primary driver of metastasis.
  • The composition of neutrophil extracellular traps suggests a mechanism for attracting and concentrating anions.
  • Targeting tumor acidity with agents like bicarbonate or weak organic acids presents a promising anticancer strategy.