A Close-Up Look at Metastasis

By Medical Discovery News

May 29, 2015

A Close-Up Look at Metastasis

One of the things that make cancer cells so deadly is metastasis, their ability to dislodge from their original location and migrate to other tissues. Most people who die of cancer are victims of this process. Even if a tumor is removed surgically, doctors can’t be certain that some of the tumor cells haven’t already metastasized, hence the need for treatments such as chemotherapy to target those cells. Unsurprisingly, metastasis is a subject of intense research, and luckily scientists now have a new tool to help them understand how tumor cells move.

While most tumors have the ability to metastasize to many different tissues, they prefer to spread to certain ones, like those in the bones, liver, and lungs. Cancer begins to spread by invading nearby tissue, then through a process called intravasation, tumor cells enter a blood or lymphatic vessel, allowing them to circulate to other parts of the body.

When tumor cells stop moving in a tiny blood vessel called a capillary, the can move out of the blood vessel and into the tissue, which is called extravasation. They will proliferate in this new location and release signals to stimulate the production of new blood vessels to satisfy the oxygen and nutrient demands of the tumor, a process called angiogenesis. Not all cells of the tumor are equally capable of metastasizing, and depending on the new environment they may not be able to grow in their new locations. In general, cells in metastatic tumors acquire additional genetic mutations that make them better able to relocate to other sites in the body. In some cancers, the metastatic cells have evolved to be remarkably different from the original tumor cells, which may contribute to the failure of treatments, the identity of the original cancer, and the recurrence of cancer.

Engineers and scientists at Johns Hopkins University have reproduced the 3-D extracellular matrix (ECM) that surrounds human cells. They also created an artificial blood vessel that runs through the matrix to simulate the flow of blood or lymph. They then added breast cancer cells either individually or in clumps.

Using fluorescent microscopy, they studied how the tumor cells interacted with the model to investigate how tumor cells get into and out of vessels, a key step in metastasis. They found that the tumor cells first dissolved some of the ECM to form a tunnel. The cells moved back and forth within this tunnel, occasionally coming into contact with the vessel. Then the cancer cells attached to the vessel through a long process, finally sitting on the surface of the blood vessel. They appear to change shape and move along the outer surface of the blood vessel. After a few days, the cancer cells force their way between the outer cells of the vessel and are swept away by the fluid moving through it.

About 60-70 percent of cancer patients are already at the stage of metastasis by the time they have been diagnosed. This new device will allow scientists to gain a better understanding of the processes and molecular players in metastasis, which will hopefully lead to new interventions or therapies that could interrupt or prevent this process.

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Ticked Off Meateaters

August 2, 2013

By Medical Discovery News

Using bug spray is more important than ever – especially for those who particularly enjoy eating hamburgers. It might sound like those two things aren’t related, but a person bitten by a certain tick can develop a severe allergy to meat.

This type of food allergy only develops in people who have been bitten by the Lone Star Tick, which has previously been linked to a condition known as Southern Tick Associated Rash Illness (STARI). The tick bite that causes this illness results in a rash, fatigue, headache, fever, and muscle pains. It is often confused with Lyme disease, which is also spread by ticks.

After being bitten by the Lone Star Tick, a person develops antibodies, which are molecules of the immune system that normally target and destroy invaders like viruses and bacteria, against a complex sugar called galactose-alpha-1,3-galactose (alpha-gal). This sugar exists in all mammals except primates, including cows, pigs, and sheep. This specific allergy has a delayed response, so a person would experience symptoms like hives four to six hours after eating a meat such as bacon. Some people even suffer life-threatening anaphylactic shock.

It is unclear what in tick saliva triggers alpha-gal antibody production. When ticks latch on to people with their mouthparts they can remain attached for several days and introduce saliva into the skin at the bite site. Tick saliva contains molecules that keep the tick firmly attached to its host. It also keeps the blood at the site from clotting so the tick can continue its meal and can influence the immune response and angiogenesis, the development of new blood vessels. In addition, ticks can transmit a variety of viruses and bacteria through their saliva.

This allergy first came to light because some cancer patients were unusually sensitive to the cancer drug cetuximab, which includes the alpha-gal molecule. But only patients from the southeastern and eastern United States, where the Lone Star Tick lives, experienced this and they all had high levels of alpha-gal antibodies. Currently, more than 80 percent of the people with this meat allergy had tick bites before exhibiting symptoms.

But now that cases of this meat allergy have been reported outside the Lone Star Tick’s habitat, such as Hawaii, researchers are wondering whether this tick has spread further than they thought, or if other tick species can cause a similar reaction. The Lone Star Tick is very aggressive when it comes to biting people and animals, so to prevent tick bites use a bug spray with permethrin, avoid wooded areas, and frequently check for ticks when outside. Otherwise, a person may find themselves watching everyone else eat during a summer barbeque!

For a link to this story, visit http://www.medicaldiscoverynews.com/shows/350-ticked.html.