Johns Hopkins Kimmel Cancer Center scientists report they have discovered a biochemical process that gives prostate cancer cells the almost unnatural ability to change their shape, squeeze into other organs and take root in other parts of the body. The scientists say their cell culture and mouse studies of the process, which involves a cancer–related protein called AIM1, suggest potential ways to intercept or reverse the ability of cancers to metastasize, or spread.

Results of the research are described in the July 26 issue of the journal Nature Communications.

For the study, the Johns Hopkins scientists mined publically available research data on the genetics and chemistry of hundreds of primary and metastatic cancers included in five studies of men with prostate cancer. They found that a gene called AIM1 (aka “absent in melanoma 1”), which makes proteins also called AIM1, is deleted in approximately 20 – 30 percent of prostate cancers confined to the gland and about 40 percent of metastatic prostate cancers. In addition, the scientists found, on average, two– to fourfold less amounts of AIM1 expression in metastatic prostate cancers compared with normal prostate cells or those from men with prostate cancers confined to the prostate, suggesting that reduction of AIM1 proteins is somehow linked to tumor spread.

The research team used dyes to track the location of AIM1 proteins in human cells grown in the lab and followed where they appear in normal and cancerous prostate tissues. In normal prostate cells, AIM1 was located along the outside border of each cell and paired up with a protein called beta–actin that helps form the cell’s cytoskeleton, or scaffolding. However, in prostate cancer cells, the protein spread away from the outer border of the cells and no longer paired up with beta–actin.

The scientists found this pattern among a set of human prostate tissue samples including 81 normal prostates, 87 localized prostate cancers and 52 prostate cancers that had spread to the lymph nodes.

With AIM1, the scaffold, Vasan Yegnasubramanian, MD, PhD, associate professor at the Kimmel Cancer Center, said, keeps normal cells in a rigid, orderly structure. Without AIM1, cells become more malleable, shapeshifting nomads that can migrate to other parts of the body, he says.

To track how these shapeshifting cancer cells move, the Johns Hopkins scientists, with Steven An, PhD, an expert in cellular mechanics and an associate professor at the Johns Hopkins Bloomberg School of Public Health, took a close–up look at AIM1–lacking prostate cancer cells, using sophisticated and quantitative single–cell analyses designed to probe the material and physical properties of the living cell and its cytoskeleton.

They found that cells lacking AIM1 remodeled their scaffolding more than twice as much as cells that had normal levels of AIM1, and that they exert three– to fourfold more force on their surroundings than cells with normal levels of the protein. Such cellular properties are reminiscent of cells with high potential to invade and migrate, An notes.

In addition, the scientists found that AIM1–lacking prostate cells were capable of migrating to unoccupied spaces on a culture dish or invading through connective tissue–like materials at rates fourfold higher than cells with normal levels of AIM1.

Next, the scientific team implanted human prostate cancer cells engineered without AIM1 in five mice and found that the cells spread to other tissues at levels 10 to 100 times more than cells with normal levels of AIM1 that were implanted in five similar mice. However, the AIM1–lacking cells were not able to establish full colonies and tumors at those other tissues, suggesting that AIM1 depletion is not the whole story in the spread and growth of metastatic prostate cancer.