Invadopods: How a Tumor Cell Becomes Invasive
To support their development, tumor cells may secrete certain enzymes that attack the surrounding connective tissues. This enables them more easily to infiltrate the interstitial tissue around the tumor, where they can grow and ultimately tear the basement membrane that surrounds and structures the organs. When this occurs, a cancer becomes invasive and more difficult to treat. In addition, once the basement membrane has been broken, cancer cells can cross into the blood vessels, enter the circulatory system, and metastasize in other organs. The enzymes, called metalloproteinases, are released by small, finger-shaped outgrowths on the tumor cells called “invadopods.”
Invadopod Formation Signals Revealed
So why not develop a drug that would prevent invadopodia from forming and contributing to the spread of tumors? Because in order to target the little-known molecular mechanisms and cell signaling involved in their development, they first need to be identified. Philippe Chavrier’s team, which specializes in the field, joined forces with another team directed by Harald Stenmark and Camilla Raiborg at Oslo University Hospital’s Institute for Cancer Research to take up the challenge.
The researchers demonstrated that a protein called Protrudin orchestrates the cell signaling that causes invadopodia to grow and function. The protein creates areas within the cell where reserves of the metalloprotease MT1-MMP, which plays a key role in tumor invasion, come into contact with the endoplasmic reticulum, a network of tubules located within the cytoplasm of the cell. This facilitates transportation of the enzyme to invadopodia. Through a technique that involved modifying the cell genome, the researchers were able to prevent the expression of Protrudin in highly invasive cells, which then lost their capacity for dissemination.
Targeting Mechanisms to Disarm Cells of Their Invasive Potential
This work has major implications for cancer treatment: targeting the processes involved in MT1-MMP transportation and storage compartment merging that allow the metalloprotease to be secreted to invadopodia could offer a new therapeutic approach that will be explored in our future research work
This collaborative effort between Institut Curie and Oslo University Hospital was conducted as part of the InvaCell project, funded through the generosity of Trond S. Paulsen.
This 3D view shows the initial step of the breaching of the basement membrane (green) by the invadopodia of invasive breast cancer cells. Invadopodia are enriched in TKS5 (red) and FYCO1 (white) proteins (NM Pedersen and C. Raiborg, University of Oslo, Oslo, Norway).