Collagen Key to Breast Cancer Metastasis

Researchers in Australia have found that a type of collagen plays a key role in regulating the tumor matrix’s organization and can even, at high levels, trigger metastasis. The study results suggest that levels of the collagen could predict cancer aggressiveness or that the collagen itself could be a potential therapeutic target.

The tumor microenvironment is the ecosystem that surrounds a tumor, one component of which is the extracellular matrix. Cancer cells constantly interact with the tumor microenvironment, which affects how a tumor grows. “Imagine cancer cells as seeds, and the tumor microenvironment as the soil,” says Thomas Cox, senior author and Head of the Matrix and Metastasis lab at Garvan Institute of Medical Research. “By studying the soil—the extracellular matrix—we can begin to understand what makes some tumors more aggressive than others, and by extension, begin to develop new ways to treat cancer.”

Collagen is an important part of the tumor microenvironment, but just how it influences tumors has not been understood.

In the study, the researchers cataloged how the tumor matrix changes over time and generated a comprehensive database of these changes, which has been made freely available to researchers. The team zeroed in on collagen XII, one of 28 types of collagen in the body. Collagen XII plays an important role in organizing other collagens and can have profound effects on the 3D structure of the extracellular matrix.

The researchers studied tumors in mouse models from the earliest preclinical stages of cancer, right through to late stage. They found that as the tumors developed, many matrix molecules changed, and importantly the level of collagen XII was also increased.

“Collagen XII seems to be altering the properties of the tumor and makes it more aggressive,” says first author Michael Papanicolaou. “It changes how collagens are organized to support cancer cells escaping from the tumor and moving to other sites like the lungs.”

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

The findings, published recently in Nature Communications, suggest that measuring the level of collagen XII 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 in the triple-negative type of breast cancer. Furthermore, collagen XII might be a possible target for future treatments.