FINDING HAS LINK TO EARLIER BREAST CANCER WORK
The research builds on earlier work begun six years ago by Kang's laboratory that looked at how several different signaling pathways promote the spread of cancer to the bone. In a study published in the journal Nature Medicine in 2009, Kang showed that a pathway known as TGF beta plays a role in the growth of bone tumors. But until the recent study, it was not clear that Jagged1 plays a crucial role in that process. Before the current work focused on identifying the series of interconnected events that create the network of destructive pathways, Kang and Nilay Sethi, a dual degree student who recently finished his Ph.D. in molecular biology at Princeton, worked to find first which of the signaling molecules were at work in patients with breast cancer that had metastasized to the bone.
"It turned out that tumor samples from patients with breast cancer that had spread to the bone had higher levels of Jagged1," said Sethi, who is now completing his medical degree at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.
The current research shows that, when the Jagged1 signaling molecule binds to its receptor molecule on the bone-producing cells, the interaction turns on the signaling pathway called Notch, and that leads to dramatic changes in bone growth. "It's like a key finding its matching lock, and opens a floodgate of information," Kang said. "Unfortunately, in this case, the Jagged1-Notch signaling is misused by cancer cells to serve a destructive purpose."
In healthy bone, specialized bone cells called osteoclasts scour the bone surface and use a combination of enzymes and acids to break down the
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