New protein found to control deadly cancer metastasis

Stopping cancer’s spread: New protein found to control deadly cancer metastasis

By Loren Grush

Published June 15, 2013
  • Metastatic breast cancer final.jpg

    This image shows metastasized human breast cancer cells (magnified 400 times, stained brown) in lymph nodes. (National Cancer Institute)

Researchers have found a critical element that may explain why some cancers spread farther and faster than others, a discovery that could lead to one of the Holy Grails of cancer treatment: containing the disease.

Scientists from the University of California, San Diego School of Medicine have identified a protein that seems to serve as a switch, regulating the spread of cancer from the primary tumor to distant spots in the body – a process known as metastasis.  The protein is used by embryo cells during early development, but then disappears from the body after an individual comes out of the womb.

According to the researchers, the protein was only found in people with metastatic cancer, leading them to belive that the regulation of this protein could potentially stop the dangerous progression of this killer disease.

“The protein seems to get turned off (after embryonic development), and we’ve only identified a small sub-population of cells that can turn it on,” lead investigator, Dr. Thomas Kipps, Evelyn and Edwin Tasch Chair in Cancer Research at UC San Diego, told  “By and large, we looked at the brain, lungs, heart, kidney and other organs, and it wasn’t there. Then we looked at a variety of cancers – breast, ovarian, prostate – and it seems to be a common theme to express this embryonic protein.”

Kipps said they stumbled upon this protein while conducting immunotherapy research on leukemia patients, in which they reengineered the patients’ leukemia cells and injected them into their bodies.  This technique is meant to enhance the body’s natural immune response to cancer.

“We did have patients respond to their leukemia cells, but part of the immune response was a cell that targeted (this protein),” Kipps said. “Anecdotally, these patients did well. So we wanted to know (what) it is doing.”

The protein, called Receptor-tyrosine-kinase-like Orphan Receptor 1, or ROR1, is involved in a process known as epithelial mesenchymal transition (EMT), which occurs during early embryonic development.  Throughout the EMT process, embryonic cells migrate and eventually grow into new organs.

Kipps explained that ROR1’s role during embryonic development may explain how it helps cancers to grow and spread.

“It’s a protein that sits on the surface of the cancer, so it has the ability to bind to other proteins outside of the cell and may have the ability to bind to other proteins on the cancer cell membrane,” Kipps said.  “Half of it sits outside the cell and half inside the cell.  It’s like having an antenna sticking out, and then you have a transmitter below the surface.  That transmitter conveys important signals to the cell, and it seems to allow itself to assume a better state of migration.”

In a series of lab experiments, Kipps and his team found that high-level expression of ROR1 in breast cancer cells were associated with higher rates of relapse and metastasis.  However, when they used therapies to silence the expression of ROR1, the researchers were successfully able to inhibit metastatic spread of the cancer cells in animal models.

“It’s like taking the antenna away; you can’t hear the radio or TV station anymore,” Kipps said. “The cancer cells become more fragile and don’t grow as well.”

After cardiovascular disease, cancer is the second leading cause of death in the United States, with 575,000 Americans dying from the disease each year. One of the scariest aspects of receiving a cancer diagnosis is learning how far the disease has spread throughout the body.  An individual’s prognosis can vary greatly depending on the extent of the cancer’s progression; if it has spread too much, modern treatments can do little to stop it. This explains why the vast majority of cancer-related deaths – approximately 90 percent – are due to metastasis of the original tumor cells.

Since ROR1 is only expressed in cancer cells, Kipps said it provides a singular target for future therapies aimed at containing and reversing metastasis.  Then, once the cancer becomes more localized, traditional therapies such as radiation and surgery can help remove the original tumor from the body.

“I think it’s an exciting time for cancer treatment,” Kipps said.  “I do think it’s a great time for discoveries, and hopefully we’ll be able to cure many forms of cancer – turning it into a bad experience rather than a life threatening event.”

The research was published in the June 15 issue of the journal Cancer Research.

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