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

La Jolla, Calif., July 3, 2014 - A team of scientists from Sanford Burnham Medical Research Institute (Sanford-Burnham) has found that the loss of a protein called p62 in the cells and tissue surrounding a tumor can enhance the growth and progression of tumors. The study suggests that therapies targeting the tumor microenvirnoment may be as important as targeting the tumor itself.

The findings, published July 3 in Cancer Cell, contribute to the increasing acknowledgement that the cells and tissue surrounding a tumorthe stromaare an integral part of cancer initiation, growth, and expansion.

"Our study reveals a precise mechanism that stromal cells use to encourage the tumorigenesis of epithelial cancer cells," said Jorge Moscat, Ph.D., director of the Cell Death and Survival Networks Program at Sanford-Burnham. "We have shown that in the stroma, p62 acts as an anti-inflammatory tumor suppressor, controlling the inflammatory environment and the signals that promote cancer. In the absence of p62, tumors grow larger and are more inclined to metastasize."

p62 location influences tumor growth

Previously, Moscat and colleagues demonstrated that p62 activation in prostate and lung cancer epithelial cells had tumor-promoting effects. Cancers of the epithelial cells are called carcinomas, and about 85 percent of all cancers are carcinomas.

In the current study, his team studied the effects of p62 in the tissue adjacent to the tumor, and found it had the reverse effects there.

"These are highly significant observations since p62 activates another protein called mTOR which is a biological target of many ongoing clinical trials in cancer right now," said Maria Diaz-Meco, Ph.D., professor at Sanford-Burnham and co-author of the study.

"This potentially means that therapeutic strategies aimed at depleting an organism of p62 and inhibiting mTOR in the cells that surround the tumor may actually benefit th
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Contact: Susan Gammon
sgammon@sanfordburnham.org
858-795-5012
Sanford-Burnham Medical Research Institute
Source:Eurekalert

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