Sun, 21 Dec 2003

Studying cancer cell behavior outside the body

Dewi Anggraeni, Contributor, Melbourne, Australia

Despite various research conducted, resulting in increasingly more successful treatment, breast cancer still invokes fear and despair in those who are told they have it.

How could it not, when every year, 182,000 women are diagnosed with it, and 43,300 die. One woman in eight either has or will develop breast cancer in her lifetime. It is undiscriminating in its attack -- any race, in any part of the world, is not safe from it. Even men are not immune to breast cancer.

In fact, the U.S.' National Cancer Institute predicted that in 2003 alone 1,600 men would be diagnosed with it, of which 400 cases would be fatal.

It is clear there is still a great deal about breast cancer which eludes researchers. So each new discovery in cancer research therefore, brings new hope.

The latest breakthrough has been achieved by Melbourne's Deakin University team led by Associate Professor Leigh Ackland, in understanding the spread of breast cancer.

The team has developed a unique breast-cell culture system which mimics many aspects of the behavior of breast cells. In other words, researchers are now able to study outside the body, how breast cells turn into cancer cells -- as it is not easy to isolate cancer cells then conduct experiments in the body without affecting healthy cells around them.

Associate Professor Ackland, who started her research nine years ago, explains her interest is focussed on what happens to cells when they become cancerous.

"In this way we hope to understand what is happening to the whole body overall," she said.

The general characteristics of cancer cells are that they tend to grow without stopping, and this leads to the formation of a mass of cells or a tumor.

However, it is worth noting that cancer cells do not necessarily grow faster than normal cells, they may even grow more slowly. But they grow continuously. While a normal cell will only divide and form new cells if they are required.

Most body organs -- like the liver, brain and kidney -- do not grow in size. New cells are produced only to replace old dead cells. Cancer cells grow and push normal cells out of the way.

Cancer cells do not have the same capabilities as normal cells. They change so often they cannot carry out the special functions that normal cells can. Sometimes they appear like immature cells.

While normal cells stay in their correct positions in their respective organs, cancer cells spread around, or metastasize to different places in the body. When this happens, according to Ackland, during a treatment procedure it is very hard to selectively get rid of the cancer cells without damaging normal cells as well.

This is where the cell culture system the researchers developed and termed PMC42-LA, plays a crucial role.

In studying cancer cells growing in culture, the researchers discovered more aggressive cells are more able to move away from their site of origin. They may make more enzymes which allow them to digest their way into the blood stream. Also, aggressive cancer cells may have altered their characteristics, or lost the capacity to function normally, and cannot interact with other cells the way normal cells should.

"Cultured human breast carcinoma cell lines are important models for investigating the development of breast cancer, but their use is limited because they usually loose the expression of breast-specific markers and develop a de-differentiated phenotype after continuous culture," Ackland explained in considerable detail.

"PMC42-LA is a unique human breast carcinoma line, previously shown to express breast cell-specific molecules. We have made PMC42-LA cells form hollow structures in culture, similar to in vivo breast structures, using a combination of hormones. The PMC42-LA structure expresses milk proteins usually found in the lactating breast. PMC42-LA is a new model for investigations into the molecular mechanisms of cancer as it represents the human breast in terms of organization of cells and production of milk proteins."

It is known that a bad environment is a factor that causes a normal cell to become cancerous.

In past experiments using animals, scientists would irradiate and damage the stromal or the extracellular environment of the mammary gland, and place normal breast cells in this environment. They found the normal cells would turn into cancer cells.

The researchers have noticed that what is in the environment of the cell can profoundly influence how the cells arrange themselves and affect their ability to make milk proteins. This is an important part of the study, because in their experiment, if they do not use an extracellular environment which has molecules usually found in the normal breast's environment, the cells will grow as a flat sheet and not organize themselves to form secretory structures.

One important advantage of research work on cells outside the body is that it is possible to see if cancer cells, thought generally to be "permanent" and having genetic modifications, can be reverted to normal, by changing their environment, thus influencing their behavior.

"Future work will let us know to what extent we can do this," Ackland said with optimism.