Princeton Researches May Have Cracked Metastatic Cancer Code

A team of Princeton University researchers may have cracked the code to figuring out how cancer metastasizes.

A team of Princeton University biologists reported Thursday they may have finally figured out the cancer’s molecular point of attack.

“Everyone knows that metastasis — the spread of cancer — is the reason people die,” Yibin Kang said. “Everyone knows it’s the most important question — but it’s been almost impossible to tackle, it’s been too complicated. It’s only very recently that we have the tools to answer the question.”

Kang and his research team discovered breast cancer tumor cells use a well-known protein and molecular pathway to essentially hijack the bone repair process, according to a paper published in the online journal Cancer Cell.

The malignant cells, they wrote, use a protein called Jagged1 and its so-called “Notch pathway” to get a stronghold in bone tissue in 70 percent to 80 percent of patients with an advanced stage of the disease. From there, the cancer spreads throughout the body.

In healthy people, cells called “osteoclasts” and “osteoblasts” naturally repair the skeleton by breaking down and rebuilding bone, like microscopic repaving machines. But in cancer patients, Kang found tumor cells use Jagged1 to commandeer the process, using the osteoclasts to forge deep into the bone and even speed up the growth of tumors there.

The researcher and his lab have made previous discoveries about the spread of breast cancer to skeletal cells. In a 2009 study, Kang showed that TGF-beta, which controls cell proliferation, played a role in the growth of bone tumors.

Jagged1, it turns out, plays a similar role in that process.

The latest work by the Princeton researchers reveals TGF-beta is released in large amounts during the breakdown of bone and feeds the tumor cells, thereby stimulating increased production of Jagged1. Together, the two processes possess considerable destructive power.

“(It) establishes a vicious cycle, essentially driving the unstoppable expansion of tumor and the destruction of skeletal tissues,” said Nilay Sethi, a student who recently finished his doctorate in molecular biology at Princeton and worked with Kang on the discovery.