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New study reveals how tumors remodel their surroundings to grow
Date:7/3/2014

e tumor, because tumor-suppressive activities would be inactivated. It also may explain why therapies aimed at blocking mTOR are showing limited clinical efficacy," added Diaz-Meco.

Unveiling the mechanism of p62

The initial hint that p62 in the stroma influences tumor growth came by analyzing more than 200 human prostate tumors with Gleason scores ranging from 2 to 10. Gleason scores are a numerical assignment given to prostate tumors based on pathology, with the highest scores (10 maximum) indicating that the cancer is very likely to spread. The research team found that p62 levels in the stroma were significantly lower in samples with the highest Gleason scores, suggesting a protective role for p62.

To understand how p62 works, the research team introduced prostate cancer cells and monitored tumor formation in normal mice, and mice genetically engineered to lack p62. The mice without p62, called p62 knockout (KO) mice, had larger prostate tumors compared to normal mice, supporting the notion that the absence of p62 in an organism promotes cancer growth.

The researchers went on to show that p62 KO mice had increased levels of IL-6, a pro-inflammatory cytokine (a signaling molecule) that enhances tumor cell proliferation and inhibits cell death. And, the genetic events that linked p62 depletion to increased levels of IL-6 in mice were mirrored in humans.

"Our observations support a more comprehensive approach to treating cancer, one that is based on our understanding of the communications between a tumor and its environment," added Moscat. "Conceivably, treatments that inhibit tumor-promoting inflammatory signals combined with tumor-specific targets may improve cancer outcomes."


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Contact: Susan Gammon
sgammon@sanfordburnham.org
858-795-5012
Sanford-Burnham Medical Research Institute
Source:Eurekalert

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