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Tumor cells engineer acidity to drive cell invasion, Moffitt Cancer Center researchers say
Date:1/24/2013

nd invasion is increased glucose metabolism in the tumor. "The vast majority of malignant tumors metabolize glucose at high rates," Gillies said. "We have proposed that there is a direct, causative link between increased glucose metabolism and the ability of cancer cells to invade and metastasize."

According to the research, elevated glucose metabolism is the cause of increased acidity in the tumor microenvironment. Most tumors develop an abnormal vascular network that tends to be poorly organized and leaky, disrupting blood flow and hampering the delivery of oxygen.

"This poorly organized vascular system has a two-fold effect on tumor acidity," explained Gatenby. "First, it subjects tumor regions to poor perfusion, which restricts oxygen and increases the rate of glucose fermentation. Second, the poor perfusion hampers the ability to eliminate the resulting acids, resulting in very low pH in surrounding tissues."

As tumor cells adapt to increasing acidity, niche engineering through normal cell death and new blood vessel formation occurs in the tumor and the immune response is suppressed.

"Tumor cells perform niche engineering by creating an acidic environment that is not toxic to the malignant cells but, through its negative effects on normal cells and tissues, promotes local invasion of malignant cells," Gatenby said.

The researchers suggested that targeting this activity with buffers and other mechanisms aimed at increasing pH levels will likely provide a valuable alternative to traditional therapies focused entirely on killing tumor cells.


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Contact: Kim Polacek
kim.polacek@moffitt.org
813-745-7408
H. Lee Moffitt Cancer Center & Research Institute
Source:Eurekalert

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