Cancer Hijacks Body's Wound-healing Process

The research, reported in the May 6 issue of the journal Cell, began when Akira Orimo, a postdoctoral scientist in Weinberg's lab, investigated the nature of stromal cells in breast cancer tumors.

Stromal cells form the connective tissue in a mammal's organs and glands. They also form the connective tissue inside tumors, which are composed mostly of cancer cells and stromal cells. Researchers wondered if the stromal cells simply hold the tumor together or if they work with cancer cells to promote the tumor's growth.

"It turns out the cancer cells are not acting alone," said Weinberg. "These stromal cells play an important role in helping these cells, and therefore tumors, to grow."

Orimo found that a particular protein produced by the stromal cells, called SDF-1, is a key player in helping tumors grow. SDF-1 interacts with a class of cells called endothelial precursor cells. Found primarily in the blood, endothelial cells travel throughout the body and aid wounded tissue by enabling new blood vessels to form, a process called angiogenesis.

The stromal cells in the breast cancer tumor produce SDF-1, which in turn persuades these endothelial precursor cells to enter the tumor. Once they do, they help the tumor to form its own robust network of blood vessels, weaving a circulatory system throughout the tumor mass. The tumor can now access the nutrients present in the host's circulating blood and can then grow unchecked.

"Essentially, these stromal cells opportunistically exploit the normal wound-healing process to benefit the tumor," said Weinberg.

Orimo plans to further investigate this process by disturbing the interactions between the stromal cells and the cancer cells, work that may yield new therapeutic insights.

Additional co-authors of the Cell paper are from the Brigham and Women's Hospital, Harvard Medical School, Massachusetts General Hospital, Baylor College of Medicine and the Institute Pasteur.

This work was funded by Merck/MIT, the National Institutes of Health, the Ludwig Trust, the Breast Cancer Research Foundation, Uehara Memorial Foundation, Sankyo Foundation of Life Science, and a U.S. Army Pre-doctoral Breast Cancer Fellowship.