by Breast cancer is a significant health concern globally, with brain metastasis being a major cause of mortality. Occurring in approximately 10% to 30% of patients with metastatic breast cancer, brain metastasis poses unique challenges due to limited treatment options and poor survival rates. In an effort to improve diagnostics and treatments, scientists at Moffitt Cancer Center have identified a crucial cell signaling pathway that controls breast cancer’s spread to the brain.
The team at Moffitt focused their research on cancer-associated fibroblasts and the process of fucosylation. Cancer-associated fibroblasts play a role in supporting and promoting cancer growth and progression within the tumor environment. While their contributions to primary breast cancer development are well-understood, their involvement in brain metastasis is less defined. Fucosylation, on the other hand, is a protein modification where the sugar L-fucose is added, affecting their behavior and functions. It is believed that high levels of fucosylated proteins are associated with breast cancer progression.
Dr. Eric Lau, an associate member of the Department of Tumor Microenvironment & Metastasis at Moffitt, explained that while studies have shown the role of fucosylation in various cancer types, including those affecting the brain, the impact of aberrantly fucosylated proteins on tumor-cancer-associated fibroblast interactions and the promotion of brain tumor progression remains unclear.
In initial lab experiments, the researchers discovered that breast cancer-associated fibroblasts exhibit heightened fucosylation levels that correlate with metastasis, indicating the potential promotion of breast cancer progression. Further investigations revealed that cancer-associated fibroblasts from breast cancer brain metastases secrete the protein poliovirus receptor (PVR), which significantly increases the migration and invasive capacity of metastatic breast cancer cells, exacerbating the invasion of breast tumors in the brain.
Crucially, the researchers found that the secretion of PVR is triggered by its fucosylation, which is facilitated by the protein FUT11 induced by hypoxia. Patient samples further confirmed that fucosylated PVR levels in cancer-associated fibroblasts from breast cancer brain metastases surpass those in breast cancer cells.
These findings strongly suggest that the fucosylation of PVR and its subsequent secretion by cancer-associated fibroblasts play a crucial role in regulating breast cancer metastasis and invasion in the brain. With these insights, the researchers hope that new diagnostic and therapeutic strategies can be developed to effectively address breast cancer brain metastasis.
Dr. Emma Adhikari, lead study author and recent Moffitt Cancer Biology Ph.D. graduate of the Lau lab, highlighted the significance of their findings by stating, “Our study provides important mechanistic insights into breast cancer brain metastasis pathogenesis, highlighting brain metastasis cancer-associated fibroblast-secreted/-fucosylated PVR and FUT11 as potential new therapeutic targets and biomarkers for breast cancer brain metastasis.”
By uncovering this pathway that controls breast cancer’s metastasis to the brain, the researchers have paved the way for further investigation and the development of targeted therapies to improve the prognosis for patients with this aggressive form of cancer.
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- Source: Coherent Market Insights, Public sources, Desk research
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