Non-Disease Virus Kills Breast Cancer Cells In Lab

 

A virus that infects humans without causing disease kills breast cancer cells in the laboratory. Researchers from Pennsylvania State University (Penn State) College of Medicine in the US, tested an unaltered form of adeno-associated virus type 2 (AAV2) on three different human breast cancer types representing different stages of cancer and found it targeted all of them. They hope by uncovering the pathways the virus uses to trigger cancer cell death, their work will lead to new targets for anti-cancer drugs. A paper on this work appeared recently in the journal Molecular Cancer.

In earlier studies, the team also showed that AAV2 promotes cell death in cervical cancer cells infected with human papillomavirus (HPV).

Cells have different ways of dying. When a healthy cell gets damaged, or starts behaving in an abnormal way, this normally triggers production of proteins that cause apoptosis or cell suicide: part of this process also involves switching off proteins that trigger cell division. The problem with cancer cells is that apoptosis fails, and the proteins that regulate cell division and proliferation stay switched on, so abnormal cells continue to multiply and create new abnormal cells and that is how tumors develop.

Breast cancer is the most common cancer in the world and the main cause of cancer-related death in women.

First author Dr Samina Alam, research associate in microbiology and immunology at Penn State, told the press in a statement released on Thursday that breast cancer is also “complex to treat”.

Senior investigator Dr Craig Meyers, professor of microbiology and immunology at Penn State, explained why:

“Because it has multiple stages, you can’t treat all the women the same. Currently, treatment of breast cancer is dependent on multiple factors such as hormone-dependency, invasiveness and metastases, drug resistance and potential toxicities.”

However, he went on to say that in their study, they showed that “AAV2, as a single entity, targets all different grades of breast cancer”.

He and his team believe that AAV2 is switching back on the apoptosis pathways that were switched off in the cancer cells.

For their study they used lab tissue cultures of cancer cells and found AAV2 killed 100% of them within seven days, with most of the cell death proteins activated on day five.

In another experiment, working with cancer cells from an aggressive form of breast cancer, they found the virus took three weeks to kill the cells.

Alam said they can see the virus is killing the cells, but exactly how it is doing it remains somewhat of a mystery.

“If we can determine which viral genes are being used, we may be able to introduce those genes into a therapeutic. If we can determine which pathways the virus is triggering, we can then screen new drugs that target those pathways. Or we may simply be able to use the virus itself,” said Alam.

They still need to do more to find out exactly how AAV2 kills the cancer cells and for instance establish which of its proteins trigger the cell death pathways.

Although AAV2 does not affect healthy cells, if it were used directly as a treatment, the human immune system would probably target it and expel it from the body. That is why the researchers think a better approach would be to find which pathways it uses and then develop drugs that use them.

Meyers has a hunch that it involves the cellular myc gene. This gene is usually linked to cell proliferation, but sometimes myc protein is known to be involved in apoptosis as well.

In their paper, he and his co-authors explain how they found increased expression of this gene close to the time of death in the breast cancer cells.

The researchers at Penn State have also found that AAV2 can kill cells derived from prostate cancer, methoselioma, squamous cell carcinoma, and melanoma.

They have also studied the effect of AAV2 on the most aggressive form of breast cancer in a mouse model; preliminary tests suggest it destroys such tumors in mice, and they will be reporting those findings soon, they said in a statement.

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