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April 26, 2006

New Insight Into 'Highway' For Cancer Spread

Topics: Medicine

If malignant tumors remained local and never spread throughout the body (metastasized), cancer wouldn't be so much of a problem. Unfortunately, malignant tumors do metastisize, and essentially build a road on which to travel throughout the body. In many solid tumors, metastasis is a major problem, and in breast, prostate, pancreatic and other cancers, while "those that are locally controlled do very well, ... those that have metastatic spread do very poorly".

Now, new research reveals how that road, which can sometimes become a "highway" in fast-growing cancers, gets built.

A key enzyme called lysyl oxidase (LOX) allows oxygen-poor, localized tumors to gain access to other sites throughout the body, "making a sort of highway for metastasis to spread," explained lead researcher Amato Giaccia, director of the department of cancer and radiation biology at Stanford University.

He called the finding exciting for two reasons: First, it helps explain how cancers make the switch from a localized to a metastatic state; and second, it points to LOX as a potent new target for drugs or vaccines aimed at arresting that lethal change.

"Based on our animal studies, it looks like it could be a very useful weapon in our arsenal against cancer," ...

Up until recently, however, scientists have known little about the mechanisms that get cancers moving.

"In other words, those things that make a tumor highly aggressive. We're finding that it's a function not only of the tumor, but also of the 'microenvironment' of the host," explained David Cheresh, a professor of pathology at the University of California, San Diego, and a leading expert in the field of metastatic cancer research.

One of these microenvironmental changes relies on an undersupply of oxygen -- a state called hypoxia -- in tumor cells.

"Solid tumors have a very ill-defined and poorly developed blood supply," Giaccia explained. In fact, many tumors become hypoxic, and experts have long noticed that hypoxic tumors are much more aggressive and prone to metastasis than more oxygen-rich cancers.

The Stanford group discovered that the hypoxic state triggers a very high expression of the gene that produces the LOX enzyme. That's important, because LOX aids metastasis by building the collagen "matrix tracks" that cancer cells travel on as they migrate to other sites.

But would inhibiting LOX curtail this migration? To find out, Giaccia's team created a human breast cancer cell line that was genetically unable to produce LOX, even under hypoxic conditions.

They then implanted these cells into mice, along with normal breast cancer cell lines.

"We showed that just by altering this single gene we could rather remarkably reduce the amount of metastatic [disease] that formed," Giaccia said. While mice with normal cancer lines went on to develop metastatic cancer, mice with LOX-disabled tumors showed no such spread.

Furthermore, antibodies aimed at LOX also inhibited cancer spread, suggesting that vaccines might someday keep the body "on guard" against the threat of metastatic disease. LOX-inhibiting drugs might do the same, Giaccia said.

Read more and learn about the possibilities for future therapeutic applications...

Posted by Richard at April 26, 2006 5:42 PM

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