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Colon Cancer Cells Use "Let Me Pass" Signals

In what reads like a chilling tale of skulduggery and subterfuge, researchers writing online in the journal Cancer Cell this week, describe how colon cancer tumor cells send "let me pass" signals to make blood vessel walls permeable, thus allowing them to travel through and establish themselves in neighbouring tissue (extravasation).

However, the discovery is good news in that it sheds a welcome light on an important question: how do tumor cells set up signalling pathways to migrate from the primary site and metastasize to other parts of the body?

Senior author Mathias Heikenwälder, a professor of virology at the Technische Universität München's (TUM) Klinikum rechts der Isar and Helmholtz Zentrum München, Germany, told the press:

"The tumor cells outwit the endothelial cells by emitting a signal used by healthy cells."

For the study, Heikenwälder and colleagues used colon cancer cell lines and tissue from mice and humans.

They found that metastatic colon cancer cells, the cells that travel and establish new tumor sites in other organs, release a chemokine called CCL2. A chemokine is a small messenger protein that sends chemical signals. Researchers first came across them when they were studying how inflammation attracts white blood cells.

CCL2 appears to act a bit like the electronic card you use to get into your hotel room, except it uses a chemical signal. When it "docks" onto the endothelial cells that line blood vessel walls, it sends a signal to the corresponding receptor (CCR2). This "opens the door" by making the endothelial cells permeable: creating a path for the tumor cells to travel through the blood vessel wall into neighbouring tissue, a process known as extravasation.

The fact that tumor cells have chemokines is not new: but the focus until this study has mainly been on how macrophage cells of the immune system use them to locate and destroy tumor cells.

By uncovering this new role of chemokines in tumor cells, Heikenwälder said they have "potentially uncovered a brand new approach to cancer treatment".

For instance, measuring levels of tumor chemokines could be a marker for how likely or quickly a primary tumor might spread to other organs, he added.

"Furthermore, the option of blocking the chemokine receptor CCR2 at the endothelial cells gives healthcare professionals a new way of preventing metastases both before and following an operation," he added.

They now plan to examine their findings in more detail and then see if they can be applied to other types of cancer.

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