Researchers map the unique proteins secreted by cancer cells

Disease and treatment 3. may 2019 4 min Professor Jens Nielsen Written by Kristian Sjøgren

Cancer cells in various tissues secrete various proteins. Researchers have now identified many of the proteins that cancer cells secrete. The discovery enables researchers to start creating diagnostic tools using a blood test that can identify almost any type of cancer.

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Many cancer researchers and doctors dream that one day they will be able to perform a simple blood test, analyse the result and tell the person that they do not have cancer anywhere in their body.

This dream of more simply and accurately diagnosing cancer has now come a step closer after researchers have catalogued the unique proteins that cancer cells in various types of tissue secrete outside the cells.

This catalogue paves the way for developing diagnostic tools that very simply analyse blood tests for biomarker proteins from such cells as those from lung, prostate or kidney cancer. This type of diagnosis using a blood test will also supersede expensive CT scans.

“This is the long-term goal. This study identified for the first time at least one protein that is unique to different types of cancer in specific types of tissue, an important step in realizing the dream,” explains the researcher behind the new study, Jens Nielsen, Professor, Department of Biology and Biological Engineering, Division of Systems and Synthetic Biology, Chalmers University of Technology, Gothenburg, Sweden.

The new study has been published in Cell Reports.

Cancer cells secrete unique proteins

Cells that mutate and become cancer cells also change their expression and their relationship with their surroundings.

For example, some cancer cells secrete enzymes that break down nearby cells or attack the proteins of other cells. Cancer cells do this to create space around them to enable them to proliferate even further.

Cancer cells can also secrete various protein-based signal peptides and change the concentrations of various proteins. The mutation into a cancer cell can change the entire complement of proteins the cell can express: the proteome.

“Becoming a cancer cell changes many metabolic processes. These cells grow faster and divide more rapidly and need space in the surrounding tissue into which they can expand. This applies to all locations, such as the lungs, skin or kidneys. The mutation into cancer cells requires many changes within the cells that are expressed through the proteins the cells secrete into the surrounding tissue. The cells change how much they produce of some proteins but also produce totally new proteins,” explains Jens Nielsen.

Finding cancer in specific sites in the body

In the new study, Jens Nielsen and colleagues catalogued the proteins that are unique to cancer cells in specific types of tissue.

For example, they discovered proteins that only cancer cells in the pancreas or colon secrete.

The cells secrete these proteins, which therefore often end up in the bloodstream, and the researchers therefore hope that they can find them in a blood test and thereby determine whether a person has, for example, cancer of the pancreas or colon.

This might be determined before the person experiences any symptoms of disease.

“At some point, we would like to be able to routinely perform one annual blood test to screen for the presence of cancer throughout the body by analysing these unique proteins that cancer cells secrete,” says Jens Nielsen.

He also explains that proteins need to be identified that are not only unique to cancer cells but also to cancer cells in specific types of tissue.

The ideal result would enable doctors to determine whether a person specifically has liver cancer, for example, and not just determine that the person has cancer in some unknown location.

“This makes our study unique. We have examined 32 types of cancer in 30 types of tissue and have identified the proteins that are specific to each type of cancer and tissue. This makes the proteins much more suitable diagnostically,” explains Jens Nielsen.

Comprehensive statistical analysis using data from genome databases

The bioinformatics-based study examined various databases of cancer samples, including from the Cancer Genome Atlas of the National Institutes of Health in the United States.

The Cancer Genome Atlas is a massive archive of samples of cancer tissue that have been whole-genome sequenced to determine their genetic structure.

Jens Nielsen and colleagues retrieved data on proteomes in the database from tissue samples from hundreds of people with cancer. More precisely, the researchers examined the transcriptomes, comprising the RNA that cells convert to proteins. RNA indicates the cellular production of proteins.

In many cases, doctors took samples of both diseased and healthy tissue from an individual, and Jens Nielsen and colleagues could then see how the proteins secreted differed between the samples. This enabled them to identify the proteins that were unique to cancer cells in specific types of tissue.

A tissue sample contains between 10,000 and 14,000 proteins. Each protein is present in varying quantities, from very few to several thousand. The researchers examined tissue samples from several hundred people with cancer for each type of cancer.

“Discovering which proteins specific cancer cells in specific types of tissue produce is actually a huge puzzle. However, we found 1 to 5 different proteins that were unique among the 32 types of cancer in 30 types of tissue, and these may form the basis for developing new diagnostic tools,” explains Jens Nielsen.

Developing diagnostic tools

The researchers are working further on developing the diagnostic tools that will enable the relevant proteins to be identified in a blood test.

Their initial goal is to examine some of the major and most problematic types of cancer.

For example, lung cancer is a very common type of cancer, and identifying it through a blood test without subjecting people to expensive scanning would be advantageous.

Another type of cancer in focus could be pancreatic cancer, which is one of the most difficult types of cancer to treat because the symptoms often appear very late in the course of the disease, when the cancer may be untreatable.

Routine screening for this type of cancer would therefore be very beneficial.

“Ultimately, we can imagine screening people at high risk of developing cancer. If a person has previously had another type of cancer, these types of screening could avoid having to scan people every 3 months. Instead, their doctor could just take a blood test and get it analysed for the proteins specific to exactly the type of cancer the person had previously,” says Jens Nielsen.

A systematic investigation of the malignant functions and diagnostic potential of the cancer secretome” has been published in Cell Reports. A main author is Jens Nielsen, Professor and Chief Scientific Officer, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark and Professor, Department of Biology and Biological Engineering, Division of Systems and Synthetic Biology, Chalmers University of Technology, Gothenburg, Sweden.

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