Wednesday, January 23, 2013

Following The Leader: Cancer Cells On The Move

One of the hallmarks of cancerous cells is their ability to uncontrollably divide and proliferate. As a result, cancer cells are notoriously hungry: the constant growth and DNA replication that takes place during their dividing frenzy requires a considerable amount of energy. They are greedy, hijacking the bodies own nutrients and resources to support their own proliferation. As a tumor increases in size and density, however, nutrients and sugar become scarce. As a result, several cancerous cells may break away from the tumor in search of greener pastures in a process known as metastasis. As they make their way to remote areas of the body, these cells must first travel through the capsule surrounding the tumor and other tissue. It takes a considerable effort to break through layer upon layer of tissue, and the strain can be too much for any one cell.


And they're off! In this video breast cancer cells (the same line used in the study, incidentally) are on the move. Cancer cells can move as quickly as 200 um/hour. Source: danielirima, YouTube user (link: http://www.youtube.com/watch?v=FPLbs-bV1L4)


A team of researchers led by Robert Austin, a professor of physics at Princeton University, found that cancer cells typically travel in a group with one cell acting as the trailblazer. The authors of the study analyzed the activity of two different breast cancer cell lines: the first line was selected for its metastatic properties, and the second formed tumors but did not metastasize. To encourage the cancerous cells to travel the researchers placed them in a chamber over a layer of collagen, a tough, fibrous structural protein. The collagen concentration used in the study was an approximation of the density of normal breast tissue. They then formed a glucose gradient: the concentration of glucose was lowest on the collagen layer where the cancerous cells were deposited, gradually increasing towards the bottom of the chamber. Glucose is a sugar which is easily converted into energy, and readily available glucose is a powerful incentive for ravenous cancer cells that need to satisfy their increased energy requirement. 

Austin and his team found that the nonmetastatic cells refused to budge regardless of glucose levels, but the higher concentration of glucose was sufficient to entice the metastatic cells to break through the collagen layer and travel to the lower glucose rich environment. The researchers filmed the cells’ movement through the chamber and observed that individual cancerous cells took turns blazing a trail for the rest of the group. As the leading cell displaced surrounding tissue, the rest of the group followed in its wake. Approximately 70 hours later another cell would take the lead. The same cell which initially led the invaders then fell back into the middle of the group, taking a well deserved break.

Scanning electron micrograph of a cancer cell migrating through the pore of a filter.  Image credit: Science Photo Library

Although it has been estimated that less than 1% of cancerous cells have the ability to metastasize, metastasis of cancerous cells accounts for almost 90% of cancer deaths. Understanding the metastatic process, therefore, may be a valuable tool in developing therapies which prevent the spread of cancerous cells and improve cancer patients’ prognoses. 

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