Abstract
Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects.
Highlights
Hypoxia is a common feature in tumors and studies have demonstrated that it promotes aggressive tumor behavior, invasiveness and metastatic potential [1,2]
As hypoxia represents a hallmark of solid tumor growth and metastasis, we aimed to study the effect of enhanced oxygenation (‘‘the flip of the coin’’), by using hyperbaric oxygen (HBO) treatment in a rat tumor model
Expression of CDH2 protein was weaker in the HBO treated, differentiated tumors and was found to be clearly increased in the less differentiated control tumors, whereas the opposite was found for CDH1 expression (Fig. 2)
Summary
Hypoxia is a common feature in tumors and studies have demonstrated that it promotes aggressive tumor behavior, invasiveness and metastatic potential [1,2]. As hypoxia represents a hallmark of solid tumor growth and metastasis, we aimed to study the effect of enhanced oxygenation (‘‘the flip of the coin’’), by using hyperbaric oxygen (HBO) treatment in a rat tumor model. The oxygen partial pressure (pO2) in tumor tissue increases significantly during HBO exposure [4] and the pO2 elevation lasts for up to 60 min post HBO treatment [5]. This type of therapy is frequently used to treat a number of diseases including carbon monoxide poisoning and nonhealing wounds [6]. Recent studies have concluded that HBO has a significant inhibitory effect per se on the growth of mammary tumors [8,9] and BT4C glioma xenografts in rats [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
