Female scientists at UBC involved in breakthrough

Researchers at the University of B.C.’s Biomedical Research Centre including student Marcia Graves and Dr. Julie Nielsen, have identified the protein that enables breast cancer cells to spread to different parts of the body. That means, they say, that pharmaceutical companies will now have a specific target to go after when they develop new drugs to fight the disease.

“We believe we’ve found a new important culprit in metastatic breast cancer, which opens up an entirely new avenue of cancer research,” said Calvin Roskelley, an associate professor of cellular and physiological science at UBC. “The culprit is hiding in plain sight on the surface of tumour cells, so we are now developing ‘smart’ molecules to block its function.”

What he and his co-investigator, Kelly McNagny, an associate professor of medical genetics, mean by the culprit is a protein that occurs on the surface of breast cancer cells that makes it possible for them to move around the body and attach themselves to different organs, such as the lymph nodes.

Researchers have known for two years that this protein, called podocalyxin, was always present on the cells of tumours that were particularly virulent and likely to metastasize. In other words, if podocalyxin was present in the tumour, it always was a signal to doctors and diagnosticians that the tumour was an especially serious one that needed to be treated aggressively with chemotherapy.

“The tumours that progressed to a really bad outcome were always the ones that had turned on this protein,” McNagny said.

But until now, he and his colleagues didn’t know why it was there or what it did.

Now they do.

With funds from the Canadian Institute of Health Research and the Canadian Breast Cancer Research Alliance, McNagny and Roskelley have discovered that podocalyxin blocks or shuts down the molecules on the surface of the breast cancer cells that these cells use to adhere to normal cells in the body.

When the adhesion molecules are blocked, cancer cells are then free to migrate around the body.

Almost all cells in the human body have adhesion molecules, McNagny explained. It is these molecules that enable individual cells to remain where they’re supposed to according to the purpose they serve. This way, liver cells remain in the liver, and kidney cells in the kidney.

In their initial stages, cancer cells also affix themselves to different parts of the body. This is how tumours become localized.

Cancer is always dangerous, but tumours are cause for particular concern when they spread or metastasize. And it is podocalyxin that makes this metastasis possible in breast-cancer cells.

Most ovarian cancers also express the protein, McNagny says, and it could be present on certain types of liver and pancreatic cancer as well.

The next step, he says, is for pharmaceutical companies to take the knowledge he and Roskelley have uncovered and use it to develop a drug specific to podocalyxin.

Such a drug could work in one of two ways, he says. Either it could shut down the protein itself or it could affix itself to the protein—that is, use it as a kind of docking device on the cell—and then kill the cancer cell from that anchored position.

“They could either find a way to block it or use as a bull’s eye,” he explained. “Since it’s on the [cell’s] surface, if we could come with a binding drug, we might be able to target toxins to these tumour cells.”

He cautions that drugs like these could still be several years away, but there is a bright side. “At least now we know how they would work.”

(From Vancouver Sun March 21, 2007)