Deceptively Cunning Cancer Cells Force Healthy Cells to Make Fake Viruses

Tumors are evolving. Some aggressive tumors are tricking normal cells to produce viruses. Image credits: iStock

With the treatment of Cancer remaining elusive, it has already one of the most frustrating diseases known to humankind.

To add to this, recently published study suggests that some aggressive cancer cells trick healthy cells to produce fake virus-like particles. This allows the tumor to grow, spread and resist treatment.

The virus mimic is detected in the blood of cancer patients, particularly in cases of an aggressive type such as triple-negative breast cancer.

However, a team of scientists from the University of Pennsylvania has deciphered this clever trick. This has opened an exciting solution to the problem by explaining how the cells behave. This could lead to a better understanding of the mechanism and bringing forth new ideas for its treatment.

THE PUZZLING PHENOMENON

Scientists predicted the behavior of some more aggressive types of cancer displaying uncharacteristically high levels of interferon-stimulated genes (ISGs). However, this is usually triggered by the presence of viruses.

Interferons are proteins made by host cells in response to pathogens such as viruses. Generally these act as a signaling system to switch on pathways that can activate an immune response. What scientists were shocked to discover was a characteristic absence of viruses in the tumors.

According to lead researcher Andy J. Minn from University of Pennsylvania, “the conundrum was that in most cases, there was no viral infection in these tumours,

Scientists were concerned because they believed that cancers with any kind of anti-viral signaling could be particularly aggressive.

Cancer cells as seen under microscope.
Aggressive cancer cells are more drug resistant. Image credits: iStock/Reddit
THE DISCOVERY

Researchers had previously found that they could encourage breast cancer cells to express ISGs by making them come into direct contact with healthy cells known as fibroblasts.

In this latest research, the team found that the fibroblasts shed tiny fluid-filled bubbles called exosomes. Interestingly these contained a type of RNA molecule normally shielded inside the cell called RN7SL1.

This particle belongs to a class of molecules that sort and secrete proteins made by the cell, something viruses do to hijack the cellular system for its own gain.

When a section of RN7SL1 is exposed through the exosome, the cancer cells believe it is the mechanisms of a virus and thus express high levels of ISG.

This boosts the cancer cell’s replication and kicks up their resistance to therapies. In return making them more aggressive and harder to kill.

HOW PSEUDO-VIRUSES CAME TO BE

Cancer cells force fibroblasts to produce pseudo-viruses by employing a signalling system to trigger the release of RNA that’s normally tucked away.

The ability of cancer cells to specifically instruct the fibroblasts to expose the viral-like end of RN7SL1 is a key discovery,” says Minn.

The research was used to pacify cancer cells. If that section of the RNA molecule could remain hidden, cancer cells wouldn’t treat the fibroblast’s exosomes like viruses.

This could lead to a treatment that could calm down more aggressive forms of cancer.

Other therapeutic targets could include the mechanism itself – a type of signal exposed on the outside of cancer cells called NOTCH. Blocking NOTCH might also prevent fibroblasts from releasing virus-like exosomes.

 

Mechanism of activation of cancer cells.
Cancer cells trick fibroblasts to produce virus-like particles. Image credits: Cell

 

Since we can test the blood of cancer patients to measure the presence of exposed RN7SL1 in exosomes, we can potentially identify patients whose cancers will be the most aggressive because of this virus mimic,” says Minn.

Now that we understand how the exposed RNA is generated, we can look to potential therapeutic targets.

CANCER TREATMENT

Tumour in triple-negative breast cancer is distinguished by a lack of receptors for estrogen, progesterone, and HER2/neu.

Without those receptors, breast cancer treatments don’t have anything to attach to. Even though chemotherapy is successful, anything that can make the tumor less aggressive and more responsive to treatment would open a lot of doors towards the cure.

The current study, along with a previous related study from Minn’s group, suggests the NOTCH pathway could be one of those potential drug targets. Drugs that block NOTCH can both turn off signals. Both that instruct fibroblasts as well as interfere with the ability of breast cancer to respond to the virus mimic.

Therapy that includes NOTCH inhibitors was effective at treating mice with triple-negative breast cancer.

However elusive the cancer treatment might be, but we are certainly heading in the right direction.

Have a look at the video to understand it better:

 

Source Cell Penn Medicine news

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