Blog: Decoding the Research

Gene identified in cancer stem cells linking lung cancer development and spread

Published: May 3rd, 2012

Researchers at the Mayo Clinic in Jacksonville, Florida have identified a single gene critical for the development and spread of lung cancer. In new research published in PLoS ONE, scientists identified MMP-10 (matrix metalloproteinase-10) as a key protein supporting the development and maintenance of lung cancer stem cells, the cells thought to be responsible for both tumor growth and the lethal metastases that spreads the tumor to other parts of the body.

What's a cancer stem cell?
Every organism arises from a single cell with the capacity to become any of the different cells types within your body. In adults, stem cells retain this ability and function as an internal maintenance and repair system, able to divide continuously to replenish themselves and other specialized cells.

Think of a tumor as an aberrant organ - one that isn't supposed to exist and has no beneficial function. Like normal organs, tumors can have a diversity of cell types, including a population of cells with stem cell-like qualities that maintain the tumor and enable it to grow and spread. These cancer stem cells have an unlimited ability to dividebut are not true stem cells.

Cancer stem cells not only play a role in maintaining a tumor, but are also thought to be a driving factor in recurrence and metastasis. Cancer stem cells are more resistant to chemotherapy than other cancer cells and can remain even after most of the tumor has been eliminated during treatment. By attacking cancer stem cells, we hope the tumor won't be able to maintain itself long term or have the ability to spread.

Targeting lung cancer stem cells
New research honed in on a specific gene, MMP-10, in lung cancer stem cells. MMP proteins play an important role in tissue remodeling by breaking down proteins. In normal processes, this includes repairing damaged tissues, growth and development, or building new blood vessels. In the case of cancer, MMP proteins can be high-jacked to degrade the environment surrounding the tumor (the stroma), the natural barrier that prevents tumors from spreading.

The researchers at the Mayo Clinic saw that lung cancer stem cells keep themselves healthy by producing high amounts of MMP-10. In addition, reducing MMP-10 in tumor models resulted in significantly lower tumor initiation and metastasis. When looking at patients, they found a correlation between higher expression of MMP-10 and higher metastasis. 

From this work, MMP-10 looks like a good target for a new type of cancer therapy against lung cancer stem cells, and possibly other types of cancer stem cells as well. One of the very interesting things about this research is the dual role of MMP-10 in both tumor initiation and metastasis, meaning we could target a single protein and hit tumors with a one-two punch.  

References:

Verline J, et al. Matrix Metalloproteinase-10 Is Required for Lung Cancer Stem Cell Maintenance, Tumor Initiation and Metastatic Potential. PLoS ONE, 2012; 7 (4): e35040