2022 0531 CSI study - New clues to liver cancer progression

Scientists find new clues to liver cancer progression

A team of researchers from College of Design and Engineeringthe N.1 Institute for Health and the Singapore Institute of Cancer Sciences at the National University of Singapore recently designed in vitro tumor models to better understand the crosstalk between liver cancer cells and their microenvironment. Using laboratory-grown liver mini-tumors co-cultured with endothelial cells – these are cells that form the lining of blood vessels – to conduct their study, the research team investigated the role of endothelial cells in the progression liver cancer.

“The conventional understanding is that endothelial cells are structural cells that form blood vessels. Our latest findings suggest that these cells also “instruct” liver cancer cells to increase production of a protein called CXCL1, which is associated with poor survival in patients with liver cancer.” explained Assistant Professor Eliza Fong, who led the research study. .

CXCL1 is a type of chemokine, which are signaling proteins secreted by cells to regulate the infiltration of different immune cells into tumors. Therefore, these molecules affect tumor immunity and may influence therapeutic outcomes in patients.

“Our results pave the way for new therapeutic targets to control tumor development and allow our team to better understand the mechanisms behind the progression of liver cancer,” added Dr. Toh Tan Boon, who is also a key member of the research team.

The team’s findings were published in the journal Biomaterials April 16, 2022.

Breakthrough in understanding liver cancer progression

Hepatocellular carcinoma (HCC) is the sixth most common cancer and remains the second leading cause of cancer worldwide. While several therapeutics have been approved in recent years to treat advanced HCC, the impact of anti-angiogenic therapy on the overall survival of patients with HCC remains elusive.

Previous studies have shown that tumor growth is facilitated by a biological process called angiogenesis (the development of blood vessels) which provides the tumor with oxygen and nutrients to grow. Unfortunately, the benefits of angiogenesis inhibitors are only temporary, after which the tumor resumes growth.

In order to find new therapeutic targets to better control tumor development, the NUS team decided to study the role of endothelial cells in cancer development using in vitro tumor models.

Unlike previously reported models that rely on the use of immortalized cancer cell lines, the NUS team incorporated patient-derived xenograft organoids and endothelial cells into their new model, which led the team to their important discovery. .

“We discovered that the ‘communication’ between liver cancer cells and endothelial cells contributes to the generation of macrophages. These immune cells are pro-inflammatory and pro-angiogenesis, potentially creating a very favorable microenvironment for tumor expansion,” explained Associate Professor Edward Chow, also a key member of the research team.

Advancing Cancer Research Using Complex Tumor Models

This latest study, which is a continuation of their previous work in 2018, highlight the importance of setting up such complex co-cultures to better understand the environment of liver cancer.

Importantly, these co-culture models may be useful for drug development studies aimed at targeting liver cancer and may also serve as valuable platforms to better understand how inflammation is promoted in cancer. of the liver and how it contributes to the progression of cancer.

In the future, the research team hopes to leverage their practical knowledge to set up such co-cultures and extend this area of ​​expertise to other types of cancer. Their research will provide an improved roadmap for studying cancer-endothelium crosstalk.

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