Cancers that are not detected and treated early typically metastasize and the secondary tumors, not the initial tumor, are usually the cause of death. Cancerous cells spread through the bloodstream. Thus, finding a way to prevent cells from the initial tumor from entering the bloodstream may be effective in stopping the deadly spread of the disease. The problem is that until recently, not much was known about the mechanism through which cells moved from the tumor into the bloodstream. The research team from London and Heidelberg have made an important contribution to solving this problem.
Pericytes are cells that wrap around blood vessels and are involved in the transfer of molecules from surrounding tissue into the blood. These pericytes produce a protein called endosialin that the researchers identified as playing an important role in allowing cancerous cells from breast cancer tumors to enter the bloodstream and spread through the body.The researchers examined endosialin by comparing normal (wild-type) mice with mice that were genetically engineered to be deficient in endosialin. They initially found that the weight and growth rate of initial breast cancer tumors was the same in both groups of mice, but there was significantly less metastasis in the endosialin-deficient mice.
The team examined this result in more detail in order to discover how endosialin was affecting metastasis. They found that endosialin did not play an important role at the site of the secondary tumors. Whatever it was doing, it was doing it at the site of the initial tumor.
They then compared the number of cancer carrying cells in the blood of the normal and endosialin-deficient mice and found that the endosialin-deficient mice had significantly fewer cancerous cells in their bloodstream. Endosialin was facilitating cell transfer from the tumor to the blood. They examined the effects of endosialin on the supporting tissue that surrounds and connects tumors and blood vessels and found no significant differences between the two groups of mice.
The researchers then carried out a series of in vitro studies and determined that endosialin was acting through direct cell-to-cell contact with the pericytes that modulate transfer of cells from the tissue to the blood through the walls of blood vessels.
This alone would be an important finding because it is the first time a specific mechanism for transferring cancerous cells from primary tumors into the bloodstream has been identified. The researchers went further, however. Endosialin may not play the same role in humans as it does in mice. If it doesn’t, identifying the endosialin mechanism in mice would give researchers an idea of what kind of thing to look for but the problem would be discovering what, if anything, is playing the endosialin role in humans.
The researchers examined in vitro samples of human breast cancer tumors and reported a number of findings that indicate endosialin plays the same or a similar role in both humans and mice. There were significantly higher levels of endosialin in cancerous tissue than in non-cancerous tissue. With the exception of a rare type of breast cancer, endosialin was not found on tumor cells but was found on pericytes. Higher levels of endosialin were found in samples that were taken from women who had suffered metastasis than in samples from women who had not. Finally, breast cancer recurrence was significantly greater for women who showed evidence of higher levels of endosialin production.
This research is important because it opens the door to developing ways to reduce endosialin or block its action thereby preventing the cancer from spreading throughout the body and reducing breast cancer mortality rates. In addition, if high levels of endosialin are a marker for increased risk of developing metastatic breast cancer, identifying women with high endosialin levels could lead to early and life-saving interventions. Further research is needed and this new research points the way.
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