Collagen a key player in breast cancer metastasis

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"Collagen type XII plays a key role in regulating the organisation of the tumour matrix ... also discovered that high levels of collagen XII can trigger breast cancer cells to spread from the tumor to other parts of the body, a process known as metastasis. ...
The research also suggests that measuring the level of collagen XII in a patient’s tumour 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. ...

The researchers studied tumors in mouse models from the earliest pre-clinical stages of cancer, right through to late-stage tumors. 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,”... “It changes how collagens are organised 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 ..."

From the abstract:

"The tumor stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumors that plays a crucial role in shaping their progression. Many desmoplastic tumors including breast cancer involve the significant accumulation of type I collagen. However, recently it has become clear that the precise distribution and organisation of matrix molecules such as collagen I is equally as important in the tumor as their abundance. Cancer-associated fibroblasts (CAFs) coexist within breast cancer tissues and play both pro- and anti-tumorigenic roles through remodelling the ECM. Here, using temporal proteomic profiling of decellularized tumors, we interrogate the evolving matrisome during breast cancer progression. We identify 4 key matrisomal clusters, and pinpoint collagen type XII as a critical component that regulates collagen type I organisation. Through combining our proteomics with single-cell transcriptomics, and genetic manipulation models, we show how CAF-secreted collagen XII alters collagen I organisation to create a pro-invasive microenvironment supporting metastatic dissemination. Finally, we show in patient cohorts that collagen XII may represent an indicator of breast cancer patients at high risk of metastatic relapse."

Collagen a key player in breast cancer metastasis | Garvan Institute of Medical Research The level of collagen type XII in breast tumours plays an important role in triggering the spread of cancer cells around the body.

Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis (open access)

Fig. 1: Proteomic profiling of decellularized breast tumours reveals dynamic changes in the matrisome