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Metastatic Breast Cancer: Does Collagen Play a Role in the Microenvironment?

By: Joshua Swore
Posted: Wednesday, September 7, 2022

Overexpression of collagen type XII may alter the structure of the extracellular matrix to promote metastasis in patients with breast cancer, according to an article published in Nature Communications. In a press release from the Garvan Institute of Medical Research, study author Thomas R. Cox, PhD, of Sydney, Australia, explained: “Imagine cancer cells as seeds, and the tumor microenvironment as the soil. 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.”

The authors implemented numerous proteomic profiling techniques to determine collagen type XII’s role in metastasis. Using liquid chromatography coupled with mass spectrometry and Western blot analysis, the group demonstrated an upregulation of collagen XII during mammary carcinoma development along with changing tumor biomechanics. The group was also able to establish that a poor prognosis in patients with breast cancer was linked to upregulation of collagen XII.

The researchers next used single-cell transcriptomics and learned that cancer-associated fibroblasts regulate collagen XII protein levels in the tumor microenvironment. CRISPR-edited cancer-associated fibroblasts overexpressing collagen XII led to an increase in stiffness of the organotypic matrices when compared with control and collagen XII knockdown experiments. The researchers then showed that collagen I organization was altered via second-harmonic generation multiphoton imaging. These experiments showed that reducing collagen XII expression led to a decrease in collagen I bundle thickness, directly correlating with a decrease in tumor stiffness. The researchers proposed that the increased rigidity of the extracellular matrix via collagen XII overexpression and collagen I structural organization is what seems to help create a microenvironment that facilitates metastasis.

Disclosure: The study authors reported no conflicts of interest.

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