Gene Involved in Cancer Spread Found

Scientists Identify a Gene on Chromosome 8 that Makes Breast Cancers More Deadly

by Jamie Conklin, Stanford University

This breast cancer is most deadly
when it spreads to other organs.

Scientists have discovered a gene that is involved in the spread of breast cancer. This discovery offers the hope for new treatments that can save lives.

Breast cancer is responsible for about a half a million deaths worldwide each year. The majority of these deaths happen because the cancer has come back after chemotherapy or because it has spread to other organs in the body.

If scientists could somehow stop the spreading of the cancer cells to other organs, it would save lives. In a new study, scientists think that they have found a gene that is critical for this ability in breast cancer cells.

This gene, called metadherin (MTDH), may help the tumor cells stick once they have spread to other organs. The scientists also found that this gene makes the cells more resistant to the drugs used in chemotherapy, helping the cancer cells to survive this treatment.

If scientists know what genes are important to the cancer cells, they can use that information to develop new treatments. They can look for certain drugs or treatments that affect those genes in the cancer cells to make it easier to get rid of the bad cells. At the very least, it could identify people whose cancer needs higher doses of chemotherapy.

Damaged DNA Causes Cancer

Cancer is almost always caused by DNA damage. To cause cancer, DNA damage needs to change the instructions in a cell. This usually happens by affecting one or more genes in that cell. This is because genes are where a cell's instructions are kept.

Imagine a gene that has instructions for making a cell stick to a certain kind of cell. Maybe it makes some sort of glue.

If there are extra copies of the gene, then more glue gets made. Once the cancer cell is free to roam around the body, it looks for a new place to land and this extra glue will help it stick.

This is how damaging a gene might affect a cancer's ability to spread. These are the sorts of genes scientists were looking for. And happened to find.

People with Advanced Breast Cancers have Extra Copies of a Gene on Chromosome 8

Some DNA changes can affect
genes and cause cancer.

Researchers analyzed the DNA of a set of human breast cancers. They found that a region on chromosome 8, called 8q22, often has extra copies in breast cancers.

When researchers analyzed two different sets of breast tumor samples, they found that the tumors that had more copies of 8q22 were more likely to metastasize, or spread to other organs in the body. This means these cancers are more deadly.

This led researchers to look at the genes that are in the 8q22 region because one or more of them might be why these cancers spread to other organs more easily. There were six genes in this region. The researchers studied these genes by adding them to cancer cells in a lab and testing the cells in mice.

The researchers added extra copies of the genes to the cancer cells one at a time and in combinations with each other. They then injected the cells into mice and looked for the cancer to spread to other organs, especially the lungs.

Only one of the six genes they tried, MTDH, made a difference in the mice. When the researchers added extra MTDH to the tumor cells, it helped the cells spread to the lungs faster than without it.

They also did the reverse experiment where they took away most of the MTDH in breast cancer cells. When they injected these cells into mice, the mice survived longer than if they injected cells without changing MTDH. So MTDH is definitely involved in making cancers spread. But how?

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MTDH Helps Cells Stick

Researchers then looked at what this gene might be doing. They found that extra MTDH helps the tumor cells to stick better to endothelial cells from the lung and bone marrow. This could be why it seems to help breast cancer spread.

But this isn't all MTDH does – it packs a double whammy. Another reason cancer can be hard to get rid of completely is that tumors can come back even after chemotherapy treatment. This makes the new tumors very hard to treat as the drugs no longer kill the cancer cells in the re-grown tumor.

The researchers also looked at whether MTDH had any effect on resistance to chemotherapy drugs. Extra MTDH meant that more chemotherapy drugs were needed to kill the cancer. Less MTDH made the cells more sensitive to chemotherapy.

A drug that affects
MTDH may someday
help treat breast
cancer, like herceptin.

The researchers then tested the chemotherapy drugs on tumors in mice. To do this, they injected the cancer cells just under the skin of some mice and allowed tumors to form. This is called a xenograft. This allows scientists to test the effect of something on an actual tumor, which you can't do in people.

In this experiment the researchers injected some mice with unchanged cancer cells, and in others they injected the same kind of cells with less MTDH. After allowing tumors of the same size to form, the researchers treated both types of tumors with chemotherapy drugs to see their effect on tumor size. They found that the tumors that started with the cells that had less MTDH shrank more after treatment. So less MTDH made the tumors more sensitive to the drugs!

So what does this all mean? Well, in a nutshell, if a patient has a tumor with extra MTDH, it's likely that they are going to have a more deadly breast cancer. The researchers found about 40% of breast tumors have extra MTDH.

Extra MTDH seems to help the tumors spread to other organs. It also helps the tumor cells survive treatment with chemotherapy drugs. Now scientists can start to use this new information in the treatment of breast cancer.

A New Drug for Breast Cancer?

Doctors in the future may be able to test to see if a patient has extra copies of MTDH and use that information to decide how to better treat the patient's breast cancer. With enough time and research, they may even be able to develop a drug or treatment that gets rid of most of the MTDH in tumors.

For example, doctors now look to see whether a patient's breast cancer is HER2 positive. HER2 is a gene that tells normal breast cells to grow and divide.

In HER2 positive breast cancer cells, too much HER2 is made and cells grow more quickly than normal. Scientists developed a drug called herceptin that targets the cells with too much HER2. Herceptin attaches to HER2 positive breast cancer cells and marks them for destruction by the patient's immune system. It also may stop the cancer cells from growing as quickly.

In the research described here, researchers found extra copies of MTDH led to breast cancers that were more likely to spread to other organs and were resistant to chemotherapy drugs. A possible new treatment could be to get rid of most of the MTDH in those cells. Or scientists could design a drug that interferes with MTDH so it can't do what it normally does.

Of course, these things would need to be tested before they could be used to treat human breast cancer. But this research brings hope for a new drug that could keep breast cancer from spreading and save lives!

Jamie Conklin

More Information

How genetics is being used to find and beat cancer

Content provided by the Department of Genetics, Stanford University.