Like dark empires bent on conquering new lands, many cancers send out cells to colonize new frontiers in the body. Certain blood-forming cells act as advance scouts for these malignant intruders, and scientists recently discovered how they help.
The findings could lead to completely new approaches to keeping cancers from spreading. Findings were published in the May 15 issue of Cancer Cell.
Jiehui Deng, left, and Hua Yu found a key step in cancer’s spread. (Photo by Walter Urie)
When cancer cells spread, or metastasize, to other parts of the body, they may find it difficult to establish colonies in healthy tissues. The biochemistry of healthy tissues keeps cancer cells from growing very well. In response, cancer cells recruit what are called myeloid cells to cajole the healthy tissue into accepting the invaders.
Normally, myeloid cells mature into different types of white blood cells. But in this case, the myeloid cells act as diplomats and send out friendly signals to convince the normal cells in the new location to welcome the cancer, so it can take root and grow.
Researchers led by Hua Yu, Ph.D., Tim Nesvig Lymphoma Research Fellow at City of Hope and associate chair in the Department of Cancer Immunotherapeutics and Tumor Immunology, and Jiehui Deng, Ph.D., postdoctoral fellow in Yu’s lab, found out how myeloid cells do their cancer-friendly work.
It all comes down to two important proteins: STAT3 and S1PR1.
STAT3 is highly activated in cancer cells.
The protein boosts cancer cell growth and shields the malignant cells from the body’s immune defenses.
S1PR1 senses molecules outside a cell and helps the cell react correctly to them.
City of Hope researchers found that S1PR1 is highly active in myeloid cells. It boosts STAT3’s activity in the body’s normal tissues when cancer also is present in the body. More active STAT3 means a welcoming environment for roaming cancer cells looking for a new place to colonize. So recruiting these myeloid cells helps cancer cells set up their new homes.
Researchers also found that blocking S1PR1 using a technique called RNA interference lowered STAT3 levels. In laboratory animal models, this reduced the likelihood that cancer cells would spread to new locations in the body.
“The exciting thing about our results is that they point to a whole new way we might be able to fight cancer,” Yu said. By targeting S1PR1 or the combination of S1PR1 and STAT3, researchers could keep cancers from spreading so they can be treated and completely eliminated where they began.
Other current or former City of Hope researchers on the study include Yong Liu, Ph.D., Hee-hyoung Lee, Ph.D., Andreas Herrmann, Ph.D., Wang Zhang, Ph.D., Chunyan Zhang, Ph.D., Shudan Shen, Ph.D., Saul J. Priceman, Ph.D., Maciej Kujawski, Ph.D., Sumanta Pal, M.D., Andrew Raubitschek, M.D., Stephen J. Forman, M.D., Robert Figlin, M.D., and Richard Jove, Ph.D. Researchers from John Wayne Cancer Institute and Shanghai Medical School at Fudan University also contributed to the study.
The study was supported by the Tim Nesvig Lymphoma Fellowship and Research Fund, the Markel/Friedman Peritoneal Ovarian Cancer Research Fund, the W. M. Keck Foundation and the National Cancer Institute. The National Natural Science Foundation Grants of China and Abcam also supported the work.
NCI grants: CA115815, CA122976, CA115674, CA33572 and CA001727.