Hyperbaric oxygen and cancer: more complex than we expected

Abstract

Hyperbaric oxygen (HBO) therapy refers to the breathing ofpure oxygen while in a sealed chamber that has been pres-surized at 1.5 to 3 times normal atmospheric pressure. Todate, HBO therapy has been applied in a series of diseaseswith potential hypoxia including decompression sickness,carbonmonoxidepoisoning,gasgangrene,osteomyelitis,andso on (http://en.wikipedia.org/wiki/Hyperbaric_medicine).However, cancer is not an indication for hyperbaric oxygenin both USA and China.Recently, Moen and Stuhr reviewed the evidence on theinfluence of HBO on cancers in past 9 years [1]. Their con-clusionwasconsistentwithtwoprevioussystemicreviewsonHBO and cancer that the use of HBO in patients with malig-nanciesisconsideredsafe.Inthisreview,theysummarizedtherelationship between hypoxia and cancer and the influence ofHBO on cell survival, angiogenesis, metastasis, chemothera-py,andradiotherapy.Finally,theyreviewedtheeffectofHBOon cancer cells of different types. Although they proposedsome explanations on the effects of HBO on cancers, themechanisms are more complex than we expected.HBO, hypoxia, and angiogenesisIt has been accepted that HBO can increase the dissolvedoxygen significantly, which may rectify the hypoxia incancers. However, HBO is often used once or twice dailyfor patients, and a hypoxic environment may form betweentwo exposures. As shown in this review, hypoxia is essentialfor the progression of cancers and related to the angiogen-esis. In addition, some studies have also shown that HBOtherapy can improve the angiogenesis after ischemic injury.Our previous study also revealed that HBO pretreatment canincrease the expression of hypoxia-inducible factor and itsdownstream factor vascular endothelial growth factor [2]which is a potent pro-angiogenic factor. Thus, HBO seemsto exert promotive effect on cancer growth.HBO and metastasisMetastasis is a complex process involving local cancer cellinvasion, entry into the blood or lymph vessels, and re-penetration and colonization at a distant site [3]. Theintegrity of vascular basement membrane (VBM) iscrucial for the cancer cell invasion. Suzuki et al. foundthat HBO enhanced transendothelial permeability in ratbrains [4]. In addition, HBO preconditioning was foundto increase the expression of matrix metalloproteinase(MMP) [5] which is may break the VBM. This maypotentiate the cancer cell invasion. Of interest, HBOtherapy may reduce the insult-induced expression ofMMP [6]. Thus, whether the effect of HBO on VBMintegrity depends on the microenvironment is not clear.If so, this may partially explain the absence of influenceof HBO on the metastasis of cancers.HBO and cancer stem cellsCancer stem cells (CSCs) are cancer cells that possesscharacteristics associated with normal stem cells, specifically