Posts Tagged ‘faculty’

Preventing cancer from forming ‘tentacles’ stops dangerous spread

Roughly 2 in 5 Canadians will develop cancer in their lifetime, and one in four of them will die of the disease. In 2014, it’s estimated that nine Canadians will die of cancer every hour. Thanks to advances in medical research and care, cancer can often be treated with high success if detected early. However, after it spreads, cancer becomes much more difficult to treat.

To spread, or “metastasize,” cancer cells must enter the blood stream or lymph system, travel through its channels, and then exit to another area or organ in the body. This final exit is the least understood part of the metastatic process. Previous research has shown cancer cells are capable of producing “invadopodia,” a type of extension that cells use to probe and change their environment. However, their significance in the escape of cancer cells from the bloodstream has been unclear.

In the study, the scientists injected fluorescent cancer cells into the bloodstream of test models, and then captured the fate of these cells using high-resolution time-lapse imaging. Results confirmed the cancer cells formed invadopodia to reach out of the bloodstream and into the tissue of the surrounding organs — they essentially formed “tentacles” that enabled the tumor cell to enter the organ. However, through genetic modification or drug treatment, the scientists were able to block the factors needed for invadopodia to form. This effectively stopped all attempts for the cancer to spread.

The study findings confirm invadopodia play a key role in the spread of cancer. Most importantly, they suggest an important new target for therapy. If a drug can be developed to prevent invadopodia from forming, it could potentially stop the spread of cancer.

“The spread of cancer works a lot like plane travel,” says lead author Dr. Hon Leong, now a Scientist at Lawson Health Research Institute and Western University. “Just as a person boards an airplane and travels to their destination, tumor cells enter the bloodstream and travel to distant organs like the liver, lungs, or brain. The hard part is getting past border control and airport security, or the vessels, when they arrive. We knew that cancer cells were somehow able to get past these barriers and spread into the organs. Now, for the first time, we know how.”

“Metastasis is the deadliest aspect of cancer, responsible for some 90% of cancer deaths,” says Dr. John Lewis, the Frank and Carla Sojonky Chair in Prostate Cancer Research at the University of Alberta. “These new insights give us both a new approach and a clinical window of opportunity to reduce or block the spread of cancer.”

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Genetics of cancer: Non-coding DNA can finally be decoded

To better understand how cancer develops, scientists strive to identify genetic factors — whether hereditary or acquired — that could serve as the catalyst or trigger for tumor progression. Until now, the genetic basis of cancers had only been examined in the coding regions of the genome, which constitutes only 2% of it. However, as recent scientific advances have shown, the other 98% is far from inactive: it includes elements that serve to regulate gene expression, and therefore should play a major role in the development of cancer.

In order to better understand this role, Louis-Jeantet professor Emmanouil Dermitzakis and his team, from the Department of Genetic and Developmental Medicine in UNIGE’s Faculty of Medicine, studied colorectal cancer, one of the most common and most deadly cancers. Indeed, each year, one million new cases are detected around the world, and for almost half of these patients, the disease will prove fatal. Using genome sequencing technology, the UNIGE geneticists compared the RNA between healthy tissue and tumor tissue from 103 patients, searching for regulatory elements present in the vast, non-coding portion of the genome that impact the development of colorectal cancer. The goal was to identify the effect, present only in cancerous tissue, of acquired mutations whose activation would have triggered the disease. This approach is totally new: it is the first study of this scale to examine the non-coding genome of cancer patients.

Unknown Mutations

The UNIGE team was able to identify two kinds of non-coding mutations that have an impact on the development of colorectal cancer. They found, on one hand, hereditary regulatory variants that are not active in healthy tissue, but are activated in tumors and seem to contribute to cancer progression. It shows that the genome we inherit not only affects our predisposition towards developing cancer, but also has an influence on its progression. On the other hand, the researchers identified effects of acquired mutations on the regulation of gene expression that affect the genesis and progression of colorectal tumors.

‘The elements responsible for the development and progression of cancers located in the non-coding genome are as important as those found in the coding regions of the genome. Therefore, analyzing genetic factors in our whole genome, and not only in the coding regions as it was done before, gives us a much more comprehensive knowledge of the genetics behind colorectal cancer,’ explains Halit Ongen, the lead author of this study. ‘We applied this completely innovative methodology to colorectal cancer, but it can be applied to understand the genetic basis of all sorts of cancers,’ underlines Professor Dermitzakis.

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