Potential Interaction of Inflammatory Hyperemia and Hyperphosphatemia in Tumorigenesis

Abstract

The present article proposes that the association of inflammation with cancer is potentially mediated by the interaction of inflammatory hyperemia and hyperphosphatemia. Hyperemia increases blood flow rate and blood volume, and hyperphosphatemia is caused by elevated serum levels of dysregulated inorganic phosphate. It is hypothesized that the interaction of inflammatory hyperemia and hyperphosphatemia circulates increased amounts of inorganic phosphate to the tumor microenvironment, where increased uptake of inorganic phosphate through sodium-phosphate cotransporters is sequestered in cells. Elevated levels of intracellular phosphorus increase biosynthesis of ribosomal RNA, leading to increased protein synthesis that supports tumor growth. The present article also proposes that the interaction of inflammatory hyperemia and hyperphosphatemia may help explain a chemopreventive mechanism associated with NSAIDs.

Lay abstract

This article proposes that extra blood flow and blood volume in inflammation combines with elevated levels of phosphate in the blood to increase phosphate circulation to the tumor microenvironment. Excess phosphate is stored in cells where it increases the biosynthesis of ribosomal RNA, which increases protein synthesis that promotes cancer growth. This article reviews a variety of evidence linking the combined effect of inflammation and hyperphosphatemia in tumorigenesis, and this mechanism may help explain cancer prevention associated with NSAIDs.

Graphical abstract

Potential interaction of inflammatory hyperemia and hyperphosphatemia in tumorigenesis. The association of inflammation and tumorigenesis (dotted arrow) is mediated by the interaction of inflammatory hyperemia and hyperphosphatemia (circular arrows) leading to tumorigenesis.

Keywords::

• cancer
• hyperphosphatemia
• inflammatory hyperemia
• melanoma
• NaPi2b
• NSAIDs
• phosphate toxicity
• solar erythema
• tumorigenesis
• UV radiation

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.