Collagen XII is likely a potential marker for patients at high risk of metastatic relapse

Collagen XII is likely a potential marker for patients at high risk of metastatic relapse

Collagen type XII plays a key role in regulating the organization of the tumor matrix, shows a new study from the Garvan Institute of Medical Research. A team of scientists led by Associate Professor Thomas Cox, head of the Matrix and Metastasis Laboratory, also discovered that high levels of collagen XII can cause breast cancer cells to spread from the tumor to other parts of the body, a process known as metastasis.

The tumor microenvironment is the ecosystem surrounding a tumor, one component of which is the extracellular matrix. Cancer cells constantly interact with the tumor microenvironment, which affects the growth of a tumor. Collagen is an important component of this tumor microenvironment, but how it affects tumors is not yet understood.

There is still much we do not know about the role of the extracellular matrix in cancer metastasis. Our study shows that collagen XII plays an important role in breast cancer progression and metastasis.”

Thomas Cox, senior study author and associate professor, Garvan Institute of Medical Research

"Think of cancer cells as seeds and the tumor microenvironment as soil. By studying the soil - the extracellular matrix - we can begin to understand what makes some tumors more aggressive than others, and thereby begin to develop new ways to treat cancer," he says.

Research also suggests that measuring collagen XII levels in a patient's tumor biopsy could potentially be used as an additional screening tool to identify aggressive breast cancers with higher rates of metastasis, such as the triple-negative type of breast cancer. Additionally, collagen XII could be a possible target for future treatments.

The study was published in the journal Nature Communications.

Collagen XII changes the tumor environment to help cancer cells invade

The extracellular matrix or “matrix” is a 3D network of approximately 300-400 core molecules, including several collagen proteins. This matrix provides structural and functional support to cells and tissues in all parts of the body.

In this study, researchers cataloged how the tumor matrix changes over time and created a comprehensive database of these changes, which was made freely available to researchers.

The team focused on collagen XII, one of 28 types of collagen in the body. Collagen XII plays an important role in the organization of other collagens and can have profound effects on the 3D structure of the extracellular matrix.

The researchers examined tumors in mouse models from the earliest preclinical cancer stages to late-stage tumors. They found that as the tumors developed, many matrix molecules changed and, above all, the collagen XII level increased.

“Collagen XII appears to change the properties of the tumor and make it more aggressive,” says lead author Michael Papanicolaou from Garvan. “It changes the way collagens are organized to help cancer cells escape from the tumor and move to other sites such as the lungs.”

The team then used genetic engineering to manipulate the production of collagen XII and studied the effects of metastasis on other organs. They found that as collagen XII levels increased, metastases also occurred. These results were then confirmed in human tumor biopsies, which showed that high levels of collagen XII are associated with higher metastasis and worse overall survival rates.

Further research will focus on examining additional human samples and investigating possible therapeutic routes.

Source:

Garvan Institute of Medical Research

Reference:

Papanicolaou, M. et al. (2022) Temporal profiling of the breast tumor microenvironment reveals collagen XII as a driver of metastasis. Nature communication. doi.org/10.1038/s41467-022-32255-7.

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