team, he aims to uncover the secrets of colon cancer biology to pursue tomorrow’s improved treatments.
All colorectal cancers are not the same. Research has identified distinct types and subtypes of colorectal cancer (CRC) based on different growth behavior. Louis Vermeulen and his team previously discovered that the non-cancerous, neighboring tissue (stroma or tumor microenvironment) plays a critical role in supporting (or suppressing) colorectal tumor growth. However, one type of CRC characterized by aggressive tumors, early metastases, and treatment resistance appears very different in one aspect: they seem unleashed from their environment.
Cancer cell mimicry
“We submitted a research proposal titled ‘Poor Prognosis Colorectal Cancers Display Self-sustained Growth by Niche-mimicry’ to the European Research Council,” says Prof. Vermeulen. “Building on our previous EU-funded work, we discovered that this aggressive CRC subtype ‘CMS4’ is not dependent on normal cells in the tumor environment. CMS4 cancer cells can actually make their own niche!”
While CMS4 tumors look like other types of colorectal cancer in pathology sections, this appearance is deceptive. CMS4 cancer cells can partially adopt features of stromal cells. “This ‘mimicry’ is at the core of our research project,” says Prof. Vermeulen. Because CMS4 can create their own niche, they have a kind of cellular plasticity. Prof. Vermeulen thinks this self-sustainability is a likely explanation for the aggressive tumor growth and may also be related to therapy resistance.
Masks off
In the next five years, Vermeulen’s research team will apply state-of-the-art research tools to uncover the true nature and differentiation mechanisms of CMS4 cells, using techniques including CRC organoid cultures, tumor mouse models, and single cell transcriptome analysis. “What biological factors are being made by those shapeshifted cancer cells? Which signaling pathways are involved?” muses Prof. Vermeulen. “If we can figure out how these cells are serving as a niche-replacement, we may ultimately identify biological targets for future treatments.”
European incentive
With an application success rate of only 12%, this year’s 313 recipients of the ERC’s Consolidator Grants will split €632 million to tackle major questions across all scientific disciplines. Prof. Maria Leptin, President of the ERC commented: “Even in times of crisis and conflict and suffering, it is our duty to keep science on track and give our brightest minds free reign to explore their ideas. We do not know today how their work might revolutionize tomorrow - we do know that they will open up new horizons, satisfy our curiosity, and most likely help us prepare for unpredictable future challenges. So, I am thrilled to see a new group of ERC grant winners receive funding for their scientific journey.”
Cancer Center Amsterdam congratulates Prof. Louis Vermeulen and wishes him success on his scientific journey!
For more information contact Prof. Louis Vermeulen
Text by Henri van de Vrugt