SRC starting grant for research on lung cancer cell migration to new sites

The SEK 22.8m awarded to researchers at our Institute comprised five project grants and one starting grant of SEK 6m. The latter went to Clotilde Wiel, for her project Defining new factors that drive lung cancer progression via metabolic profiling of the aging metastatic environment. Among our researchers, it was Wiel who received the largest grant in this grant application round. See the full list of all project grants in the fact box at the bottom of this article.

Image

Understanding how cancer cells spread is crucial to new forms of treatment

“It’s been shown that even before they metastasize, cancer cells prepare by secreting factors that make it easier for them to attach and grow in new sites in the body — ‘metastatic niches’, as we call them. Cells of many different types at the new site are affected and it’s known that the patient’s age, for instance, affects the composition of cells. But this needs to be surveyed further,” explains Clotilde Wiel, researcher in Surgery at the Institute of Clinical Sciences.

Lung cancer has the highest mortality rate of all cancers worldwide. This is mainly because it is diagnosed so late. By the time of diagnosis, some 50 percent of patients already have metastases.

“My previous work on antioxidants led me on to the pathways in which lung cancer can spread and form daughter tumors. Today, there are still no treatments focusing specifically on preventing tumor cells from spreading and forming new daughter tumors (metastases). Further investigation and understanding of these processes are needed. I see an opportunity to contribute new knowledge that, in the long run, may benefit lung cancer patients,” Wiel says.

She is hoping to contribute knowledge about key biological processes involved in how cancer metastasizes from its original site to a new, alien niche.

"Only when we know how cancer cells spread, and what they need to be able to do so, can we design therapies to stop them," she adds.

“We’re tremendously glad that Clotilde Wiel has chosen to set up her research project with us. Her work, focusing on metastasis in lung cancer, will create good synergies in our platform for precision medicine in lung cancer therapy. We have high hopes and big visions of going from preclinical cell environments to clinical trials, which may eventually lead to new cancer treatments, the goal being to raise survival rates and quality of life for patients with cancer,” says Volkan Sayin, researcher and head of the Precision Medicine group at the Sahlgrenska Center for Cancer Research.

Peter Naredi, who heads the Institute of Clinical Sciences, fully shares Sayin's pleasure and hopes about managing to recruit Clotilde Wiel to the Institute.

More about cancer cells’ metastatic ability

Immune cells can either counteract or assist cancer cells’ survival

When cancer cells spread, they are exposed to various types of stress, such as different environments and elevated levels of harmful free radicals known as reactive oxygen species (ROS). This exacerbates oxidative stress.

ROS and oxidative stress have been shown to hinder cancer growth and metastasis. However, cancer cells find ways to circumvent this obstacle. For example, they activate Nrf2, a protein that boosts antioxidant production in cells.

“We’ve previously shown that antioxidants promote metastasis of lung cancer,” Sayin says.

Only a few cancer cells that leave the lung tumor can grow effectively elsewhere in the body. Metastasis takes place only if these cells find an organ where they can become established, survive and grow: the metastatic niche. This niche is complex, with a heterogeneous composition that makes it hard to study. It consists of several separate cell types, including immune cells that either counteract or assist the survival of cancer cells.

Cancer cells communicate with their new home

Even before cancer cells arrive at their new location, they secrete factors that alter the environment in the target organ, causing a premetastatic niche to form. Thus, the cancer cells communicate with their new home.

“The cancer cells’ chances of survival are likely to increase if the environments they’re exposed to during their migration, including the metastatic niche, have low ROS levels. The person’s age is one of the factors affecting niche composition.”

Whether the stimulating effect of antioxidants on metastasis also includes the influence of the niche remains unknown. Nor is it known how far age and ROS influence communication between the cancer cells and the metastatic niche. Much more research is needed to understand how antioxidants affect cancer cells and the environments surrounding them during metastasis, and to identify new, underlying mechanisms in this process.

“The aims of my project,” Wiel says, “are to identify metabolic adaptations that help cancer cells survive the metastatic process and to investigate how oxidative stress, antioxidants and age affect the composition of the metastatic niche. The overall goal is for this knowledge to pave the way for new cancer treatments.”