Investigators at Sanford-Burnham identifies a mechanism in the tumor microenvironment that triggers an inflammatory response, promoting tumor growth and metastasis. The findings, published in Cancer Cell, indicate a new path to anticancer therapies that incorporates targets in the tumor stroma.

Scientists 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. It supports the conception that therapies targeting the tumor microenvironment may be as important as targeting the tumor itself.

In the current research,  Ph.D. Jorge Moscat at Sanford-Burnham found p62 in the tissue adjacent to the tumor had the anticancer effects. However, his team previously demonstrated an opposite conclusion that p62 activation in prostate and lung cancer epithelial cells had tumor-promoting effects.

“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, 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 the tumor, because tumor-suppressive activities would be inactivated.” said Maria Diaz-Meco, co-author of the study.

Uncover the mechanism of 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.