Study suggests new approach to explain cancer growth: low oxygen levels

[OKIsItJustMe]

http://news.uga.edu/releases/article/study-suggests-new-approach-to-explain-cancer-growth-low-oxygen-levels/

[font face=Serif][font size=5]Study suggests new approach to explain cancer growth: low oxygen levels[/font]

May 3, 2012

[font size=3]Athens, Ga. - Low oxygen levels in cells may be a primary cause of uncontrollable tumor growth in some cancers, according to a new University of Georgia study. The authors' findings run counter to widely accepted beliefs that genetic mutations are responsible for cancer growth.

If hypoxia, or low oxygen levels in cells, is proven to be a key driver of certain types of cancer, treatment plans for curing the malignant growth could change in significant ways, said Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the Franklin College of Arts and Sciences.

The research team analyzed samples of messenger RNA data-also called transcriptomic data-from seven different cancer types in a publicly available database. They found that long-term lack of oxygen in cells may be a key driver of cancer growth. The study was published in the early online edition of the Journal of Molecular Cell Biology.

Previous studies have linked low oxygen levels in cells as a contributing factor in cancer development, but not as the driving force for cancer growth. High incidence rates of cancer around the world cannot be explained by chance genetic mutations alone, Xu said. He added that bioinformatics, which melds biology and computational science, has allowed researchers to see cancer in a new light. Gene-level mutations may give cancer cells a competitive edge over healthy cells, but the proposed new cancer growth model does not require the presence of common malfunctions such as a sudden proliferation of oncogenes, precursors to cancer cells.

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http://dx.doi.org/10.1093/jmcb/mjs017

[dkf]

1. So why do cells have low oxygen levels?

[OKIsItJustMe]

2. From the letter…

http://dx.doi.org/10.1093/jmcb/mjs017

[font face=Serif][font size=5]Hypoxia and miscoupling between reduced energy efficiency and signaling to cell proliferation drive cancer to grow increasingly faster[/font]

[font size=4]Dear Editor,[/font]

[font size=3]The question we address here is what drives cancer to grow in an accelerated fashion as it evolves. Various proposals have been made regarding the possible drivers of cancer growth such as driver mutations and autonomous growth signaling_ENREF_1. While these are clearly relevant, they rely too much on specific types of genomic mutations or molecular abnormalities by chance across different cancer types, which makes the probability for cancer to occur/progress significantly lower than what we have witnessed about the current cancer occurrence rates world- wide, hence making them less probable to be the ultimate drivers of cancer growth (Loeb, 1998).

We present here a model for the (accelerated) growth of a cancer based on the discovered gene-expression patterns derived from genome-scale transcriptomic data of seven solid carcinoma types, namely breast, kidney, liver, lung, ovary, pancreatic and stomach cancers. Our data analysis clearly indicates that as a cancer advances, (i) its percentage of cells in the G0 phase of the cell cycle tends to become increasingly lower, indicating accelerated cell proliferation; (ii) when the hypoxia level goes up, the activity level of oxidative phosphorylation as the main energy (ATP) producer goes down and that of glycolysis goes up, which triggers cancer cells to accelerate the uptake of glucose from the blood circulation to make up for the lost efficiency in energy production, needed for them to stay viable; (iii) this switch in energy metabolisms leads to accelerated cell proliferation and further increased hypoxia, forming a vicious cycle of (accelerated) growth of cancer; (iv) this cycle breaks down when the new angiogenesis takes place triggered by the high hypoxia level, which decreases the hypoxia level and switches back to oxidative phosphorylation as the main energy producer and continues until the cells become too hypoxic again; and (v) the cellular hypoxia level goes up and down “periodically” that coincides with the increasing cancer mass and new angiogenesis, respectively, while its overall trend is going up.

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In summary, as a cancer evolves, the hypoxia level has an overall up-going trend, which drives cell division to go faster, but the cell division rate may go down from time to time due to new angiogenesis. During such a downwards period, cell division slows down and the cells prepare for material and energy needed for the next rapid growth phase. Overall the driving force of cancer growth comes from the combination of two factors: hypoxia and the miscoupling between the increased uptake of nutrients triggered by reduced energy efficiency and cell proliferation signaling induced by increased accumulation of nutrients (Figure 1G). Hypoxia might have made the further transition from a fast growing cell to cancer cells possible since it can induce a number of cancer hallmark capabilities such as activation of emergency DNA repair mechanism, which leads to increased DNA mutations, inhibition of apoptosis and activation of angiogenesis. We have noted from the public gene expression datasets (Poola et al., 2005) that precancerous tissues could be highly hypoxic (data not shown), making it possible for hypoxia to be an early key driver of cancer. Recent studies have linked a number of factors such as long-term inflammation (Eltzschig et al., 2011) that may cause cellular hypoxia, which fits well with our model here.

We believe that this model, while coarse in nature, captures the essence of the key driving force of the accelerated cell cycle, as well as the growth patterns as a cancer progresses. The actual growth rate and pattern of a specific cancer may also depend on other factors such as the cancer location and activity levels of apoptosis and immune responses. This model will provide a useful framework for experimental studies of cancer cells, as well as for building predictive models for cell growth that will take into consideration other contributing factors.

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[dkf]

3. Lol...so it's not from sitting on your butt all day long?

I have no idea what all that means in terms of what a person can do to remedy the situation.

[SolutionisSolidarity]

4. Of the posted material, the only snippet I saw that addresses your question is this:

"Recent studies have linked a number of factors such as long-term inflammation (Eltzschig et al., 2011) that may cause cellular hypoxia".

So, there you go. Just stop suffering from inflammation.