Biglycan in the Tumor Microenvironment May Act As Metastasis Trigger

A small proteoglycan secreted from endothelial cells within the tumor microenvironment has been linked to the likelihood of the primary tumor metastasizing and freeing cells to travel to other parts of the body.

Investigators at Hokkaido University (Japan) had demonstrated earlier that features of tumor endothelial cells (TECs) were different depending on tumor malignancy, suggesting that TECs communicated with surrounding tumor cells. However, the mechanism of this communication, especially its relation to metastasis, had not been elucidated.

In the current study, which was published in the June 13, 2016, online edition of the journal Scientific Reports, the investigators described the role of biglycan on tumor metastasis. Biglycan is a small leucine-rich repeat proteoglycan (SLRP) which is found in a variety of extracellular matrix tissues, including bone, cartilage, and tendon. In humans, biglycan is encoded by the BGN gene, which is located on the X chromosome. Biglycan consists of a protein core containing leucine-rich repeat regions and two glycosaminoglycan (GAG) chains consisting of either chondroitin sulfate (CS) or dermatan sulfate (DS), with DS being more abundant in most connective tissues.

The investigators reported that high biglycan expression was associated with poor prognosis in patients with breast, lung, and colorectal cancer. High levels of biglycan were found in the blood of patients with metastatic cancer, while the molecule was barely detectable in the non-metastatic disease.

The investigators also worked with mouse models of low-metastatic (LM) and high-metastatic (HM) melanoma tumors. They found that co-implantation of TECs isolated from highly metastatic tumors accelerated lung metastases of low metastatic tumors. Biglycan synthesis was upregulated by DNA demethylation in TECs, which secreted the substance, activating tumor cell migration via nuclear factor-kappaB.

The investigators said, "The present observations, together with unravelling certain remaining issues, may contribute to establishing accurate diagnostics or potent anti-metastatic strategies that target the communications between tumor cells and endothelial cells."

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