Fighting cancer at an early stage

In Sweden, every third person will be diagnosed with cancer. Estimations predict that within 25 years this number will increase to become every second person. One of the major challenges in the war against cancer is to find and treat the cancer at an early stage. Professor Anette Gjörloff Wingren and her team, including PHI’s industrial doctoral student Louise Sternbæk, are exploring ways of achieving this.

Almost half a million people in Sweden, live with a cancer diagnosis. Every year 66 000 people are being diagnosed with cancer, and this number will double within the following 25 years. It is thus well motivated to invest in cancer research to reduce the cost of future healthcare by developing new methods to detect cancer at an earlier stage when cancer is easier and less expensive to treat.

At Malmö University, Sweden, a new interdisciplinary project is ongoing where biologists and chemists work together. The researchers have developed plastic nanoparticles - Molecularly Imprinted Polymers (MIPs) – designed to perfectly fit the surface of cancer cells. On the surface of every cancer cell there are certain carbohydrate molecules, glycans. Compared to normal cells, cancer cells have more of these molecules, and the very dangerous aggressive metastatic cancer cells have even more. The small MIPs make it is possible to detect cancer cells which have these glycans on their surface and to study their behavior by using HoloMonitor imaging technology from Phase Holographic Imaging (PHI).

A HoloMonitor M4 image of cancer cells with molecular imprinted polymers (MIPs) attached to the cell surface. The optical thickness is color coded. With increasing thickness, color changes from black through red to blue.

Professor Anette Gjörloff Wingren leads a team of researchers working with a way to find cancer cells. Every cell, especially cancer cells and metastatic cancer cells, have glycans on the surface. A team of chemists at the Federal Institute for Materials Research and Testing in Germany (BAM) are designing specific nanoprobes, or plastic antibodies called MIPs. Their chemical bindings fit the cancer cell’s surface perfectly.

Anette, what are the aims with the EU project GlycoImaging?

“A major challenge with cancer is to find it and diagnose the disease at an early stage. Cancer develops in several steps. First several errors need to occur during cell division. Then the errors need to develop into cancer cells, and later turn into metastatic cancer cells. It is of great importance to find cancer at an early stage; the prognosis of successfully treating cancer is much better when cancer is detected early. The project we are working on aim to detect cancer cells and see them through real-time visualization. This is a great possibility for low-cost clinical diagnostics in a near future.”

How will you find cancer cells at an early stage?

“Traditionally, cancer cells are detected by using antibodies that attach to the surface of the cancer cells in a microscope. Antibodies are naturally created by the immune system of a living organism when it reacts to some foreign biochemical compound. However, glycans are present in varying degree on the surface of all cells. Immune systems therefore do not perceive glycans as foreign and will thus not create glycan specific antibodies. Contrary, MIPs are synthetically created in laboratory, making it possible to design MIPs that attach to any type of biochemical compound, including glycans. This is why MIPs are called synthetic or plastic antibodies.”

Professor Anette Gjörloff Wingren recently gave a rather ansual presentation of the GlycoImaging project at Almedalsveckan (in Swedish).

How cancer starts

All cancer begins in cells. Every time a cell divides, the DNA inside the cell’s nucleus replicates. This happens every day, every second in our bodies; most of the times without any disorders. For cancer to start one single error is not enough; several errors in the cell’s DNA during repeated cell divisions need to occur for cancer to develop. Additionally, the accumulated errors must affect the proteins inside the cell to develop an over-activated cell.

Usually, the immune system finds old or damaged cells and destroy them. But, if the immune system is compromised and weak for some reason the risk of developing cancer increases.

But it is not that simple. A healthy immune system does not guarantee that cancer will not develop. Cancer cells do everything they can to not be recognized by the body’s immune system; they hide or mimic normal cells. Cancer cells can also divide so fast that the immune system simply lacks the capacity to destroy all the new cancer cells, just like an explosive bacterial infection can overwhelm the immune system.

Detecting cancer

The most dangerous cancer cells are metastatic cancer cells. They are the cancer cells that spread the cancer by creating new tumors elsewhere in the patient’s body. Often these cells move through the blood circulatory system to the lungs, bones, lymph nodes, liver or the brain. These cancer cells are the most difficult cancer cells to find.

The GlycoImaging project aim to develop improved methods to detect metastatic cancer cells by using MIP and HoloMonitor technology, opening the possibility of an early screening method that can detect cancer through a simple blood sample. Cancer is today diagnosed by examining surgically removed tissue samples from the patient. Read more about the GlycoImaging project here.

How does HoloMonitor M4 help you in your research?

“HoloMonitor M4 is a fantastic tool to learn more about cellular behavior. We can see cell behavior in dying cells and follow morphological transformations throughout the entire process. The next step could be to load the MIPs with a toxic substance, and use HoloMonitor M4 to see how the cells behave, for example die, after the toxic contact.”

What do you think this project could lead to in the future?

“Cancer cells are difficult to find. They divide rapidly and hide from the immune system. Our goal is to create better methods to find cancer cells, not just in the lab but also in blood samples from patients. In the future, clinics could be using HoloMonitor to see and learn how different cancer cells behave and react to different cancer treatments. You can get beautiful images and recordings of the cells morphological behavior, combined with important quantitative data such as volume, thickness and area. I also think it’s possible to use HoloMonitor in other cell research areas such as autoimmune diseases and other diseases where cells change and need treatment.”

Louise Sternbæk
Industrial Doctoral Student at PHI

Louise, can you describe your background?

“I’m from Denmark. I have a Bachelor’s Degree in Biomedical Laboratory Science from Copenhagen University College and a Master’s Degree in Biomedical Methods and Technology from Malmö University. One of my focus areas was Immunology. I applied for a PhD position at PHI who runs this EU project together with Malmö University.”

Tell me more about the GlycoImaging project.

“The aim with the GlycoImaging project is to able to diagnose cancer in an early stage. We cooperate with a group of chemists at the Federal Institute for Materials Research and Testing in Germany (BAM). They design the MIPs we use to detect cancer cells. We are now testing the MIPs on specific cancer cell to confirm that they are finding the right cancer cells and to see how firmly they attach to the cancer cells.”

How do the MIPs find the cancer cell?

“They are perfectly designed to fit the surface of the cancer cells, and they are drawn to the glycans you find on all cells surfaces, but especially on the surface of cancer cells. Chemical bonds also make the cancer cell and MIP connect. HoloMonitor allow me to detect the small MIP particles attached to the cancer cells.”

In what way does HoloMonitor M4 help you in your research?

“HoloMonitor helps me with the essential information. I can see in what way cancer cells react to toxic substances; I can see how fast the cells react to the toxic substances and track how the MIPs find the cancer cells. It’s really great! The ability to visualize cell divisions, migration and the cells morphological behavior is also of great value.”

If you didn’t have the HoloMonitor M4, how would you solve this problem then?

“I wouldn’t. Without HoloMonitor I wouldn’t have the very important live view. HoloMonitor is a really nice tool. You start testing your cell cultures while they are inside the incubator and then leave to grab a cup of coffee. It’s very simple to use! And when the tests are done, you get the data, images and the time-lapse recordings.”

What do you think about the future?

“In the near future we’ll be able to predict which medicine that will work best for each patient’s cancer. Cancer is personal disease; all cancers are different. Today, when two patients receive the same diagnose they are treated in the same way. It will become possible to find out which cancer treatment to use for a specific person’s cancer. This approach has the potential to become very rapid, efficient and would save a lot of money in cancer care and cancer treatment.”