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Cancer cell mechanism found to be used against itself (article in BBA by LION postdoc Lena Beletkaia, PhD student Wim Pomp, and PI Thomas Schmidt and colleagues)

[18-01-2016]

(By: LION/EA)
Leiden biophysicists have found a new possible way to attack cancer cells. They have located ‘sinkholes’ on the cells where receptor proteins disappear from the surface. If a drug could push these proteins towards those areas, it would kill the cancer cell. Publication in BBA.

Weak spots
In order to find a treatment for cancer, scientists need to do fundamental research to understand the inner workings of cancer cells. Then they can identify any weak spots and ask pharmaceutical researchers to find a drug that attacks the cells at their Achilles heel. For this reason, Professor Thomas Schmidt and his group studied receptors called CXCR4 on a bone cancer cell. Those receptors perform their job on their host cell’s surface; directing the cell towards a specific place inside the human body. Metastatic cells need such receptors on their surface, otherwise they won’t know where to go and stay at the original tumor.

Adaptation mechanism
When CXCR4 proteins receive a signal from some part of our body, they become activated and lead their host cell in the right direction. If a strong signal activates those receptors, cells use a mechanism that removes receptors from their surface, so they don’t become too sensitive. A similar adaptation happens when your pupil constricts if you look at the sun. Also your ears work this way; we perceive sounds that are ten times louder than street noise only as two times as loud.

Sinkholes
Now lead author Elena Beletkaia and her colleagues have located ‘sinkhole’ areas on the bone cancer cell’s surface. Here the CXCR4 receptors sink down into the inner cell, or in biophysicists’ terms, get immobilized. ‘Doctors find that if patients have a high number of CXCR4, it is a bad prognosis,’ says Schmidt. ‘One of their ideas is to develop a drug against CXCR4, to silence them. But now that we know where the receptors disappear from the surface, there could be a different kind of intervention: push the receptors into the sinkhole, and then they are gone.’

Fluorescence microscopy
The researchers used epi-fluorescence microscopy to study their samples. This technique enables them to see individual molecules by highlighting a few of them each time they take a picture. For every snapshot they make different molecules fluorescent, causing them to emit light at a specific wavelength. This is easily filtered out from the indistinguishable noise from the many other molecules. They keep repeating this process until most molecules are located. Using this technique, the group was able to trace CXCR4 receptors and spot the location of their sinkhole hide-out.

CXCR4-receptors (purple stripes) on a cancer cell’s surface (series orange stripes) prove to move towards specific areas to disappear when they receive a strong signal. Leiden biophysicists have located these ‘sinkholes’ (indentation right). Here, the receptors sink towards the inner cell.

 

 

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