Aug 10, 2022
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Collagen is a key player in breast cancer metastasis

Collagen is a key player in breast cancer metastasis

Collagen type XII plays a key role in regulating the organization of the tumor matrix, a new study from the Garvan Institute for Medical Research has found. The team, led by Associate Professor Thomas Cox, head of the Matrix and Metastasis Laboratory, also found 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 the tumor, one of the components of which is the extracellular matrix. Cancer cells constantly interact with the microenvironment of the tumor, which affects its growth. Collagen is an important part of this tumor microenvironment, but exactly how it affects tumors is still not 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 the progression and metastasis of breast cancer. Imagine that cancer cells are seeds and the tumor microenvironment is soil. By studying soil – extracellular matrix – we can begin to understand what makes some tumors more aggressive than others, and therefore begin to develop new ways to treat cancer,” said study senior author Associate Professor Thomas Cox.

The study also suggests that measuring collagen XII levels in a patient’s tumor biopsy could be used as an additional screening tool to detect aggressive breast cancer with a higher metastasis rate, such as triple-negative breast cancer. In addition, collagen XII may be a possible target for future treatments.

The study is published in the journal Nature Communications.

In this study, the scientists cataloged how the tumor matrix changes over time and created a comprehensive database of these changes that was made freely available to researchers. The team focused on collagen XII, one of the 28 types of collagen in the body. Collagen XII plays an important role in the organization of other collagens and can have a profound effect on the three-dimensional structure of the extracellular matrix.

The researchers studied tumors in mouse models ranging from the earliest preclinical stages of cancer to advanced tumors. They found that as tumors developed, many of the matrix molecules changed and, importantly, collagen XII levels also increased.

“It appears that collagen XII alters the properties of the tumor and makes it more aggressive,” said first author Michael Papanicolaou of Garvan. “It changes the organization of collagens to support cancer cells leaving the tumor and moving to other places, like the lungs.”

The team then used genetic engineering to manipulate the production of collagen XII and looked at the consequences of metastasizing to other organs. They found that as collagen XII levels increased, so did metastasis. These results were then confirmed in human tumor biopsies, which showed that high levels of collagen XII were associated with higher metastasis rates and worse overall survival.

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