Hypoxia in prostate cancer

Peter Vaupel

Department of Radiation Oncology and Radiotherapy, Tumor Pathophysiology Group, University Medical Center, Mainz 55131,Germany.

Dear Editor,

I have read with great interest the review “Current challenges and opportunities in treating hypoxic prostate tumors” by McKenna et al.[1]. In this review, the authors present, as a key information in Table 1 of their article, values of oxygen partial pressures (pO2) in human tumors and the respective normal tissues,published earlier by our group[2,3]and “adapted” by McKeown[4]later.

In their article, McKenna et al.[1]have reviewed current knowledge about the impact of the “hallmark feature”hypoxia on pathways promoting cancer growth, malignant progression, therapeutic resistance and tumor immune escape[5-7]. Certainly, this information is of utmost interest to experimental and clinical oncologists.However, since this review contains some misleading/inappropriate oxygenation data, some additional information that may be of interest for the distinguished readership of this highly reputed journal, may serve for clarification.

In Table 1 of their review, McKenna et al.[1]present oxygen partial pressure (pO2) values together with oxygen concentration (cO2) data. When reviewing the biological role of hypoxia in malignant tumors, authors lacking an expertise in respiratory physiology often convert - without any need - the in vivo pO2values,originally measured in tumors (and in normal tissues) using pO2histography[2], into O2concentrations using either Dalton’s law (only valid for gas mixtures within the airways) or Henry’s law for gases dissolved in solutions, which cannot describe the relationship between partial pressures and concentrations of gases in heterogeneous media (e.g., tissues with lipid-rich membranes, the cytosol and the extracellular space, the latter with a high content of free water in cancers). Therefore, it is strongly suggested to avoid any conversion of measured pO2values into cO2data since the O2solubility coefficient is: (1) highly dependent on the tissue water content; and (2) usually not known for heterogeneous cancer tissues in patients. In this context, it has to be mentioned that authors not familiar with respiratory physiology often use “local O2concentrations” by mistake, although pO2values have been measured in the original studies[2,3](for typical examples see Table 1 in the review by McKenna et al.[1]).

Considering Henry’s law (cO2= α × pO2; α: oxygen solubility coefficient), McKenna et al.[1]have communicated questionable oxygenation data grounded on wrong/doubtful O2solubility values for malignant and normal tissues, which originally have been communicated for blood plasma, i.e., irrelevant data when heterogeneous tissues such as prostate cancer are considered[8].

Oxygen solubility coefficients for heterogeneous tissues (e.g., for experimental tumors[9]) are significantly lower than those for blood or blood plasma[10]. Due to this misconception, the O2concentration data of Table 1 in the review by McKenna et al.[1]are misleading/not correct and should, therefore, be removed from the table.There is no need to present concentration data in this comprehensive review.

DECLARATIONS

Authors’ contributions

Vaupel P contributed solely to the paper.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.

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Copyright

© The Author 2018.