Despite the availability of many therapies, breast cancer is still the second leading cause of cancer-related deaths in women in the USA. In a recent discovery, scientists at Pennsylvania State University and Henan University in China found a new protein marker that could potentially predict the progression of breast cancer or be targeted by drugs designed to treat the disease.
The protein called PAD4, which exists in abundance in neutrophils, is key in the immune response against bacteria. The researchers found that its expression in cancer cells can also promote breast cancer metastasis in mice, according to a new study published in the journal Molecular Cancer Research. It mediates the formation of a loosened DNA and protein structure outside the cell called neutrophil extracellular traps (NETs). Normally, NETs trap and kill bacteria. Recent studies have also found that NETs play a part in promoting cancer metastasis.
The Penn State and Henan team set out to study whether PAD4 can trigger a similar process in breast cancer cells including tumour growth and metastasis. The team found human breast cancer cells have higher PAD4 expression than do normal cells. In a triple-negative breast cancer cell line called 4T1, the researchers also observed even bigger PAD4 levels than what existed in other cell lines. Additional analysis showed that the activation of PAD4 in 4T1 cells also led to the release of chromatin fibres outside to form NET-like structures. The researchers called them cancer extracellular chromatin networks (CECNs) and found that CECN formation is dependent on PAD4, as treating the 4T1 cells with a pan-PAD inhibitor or knocking it out prevented the release of CECNs.
PAD4 may offer a novel approach to tackling breast cancer. Although further investigation is needed, it is interesting to consider the possibility that PAD4 or CECNs could potentially be used as biomarkers to predict disease progression. In addition, therapies to inhibit PAD4 or eliminate CECNs could be explored as a method to reduce the risk of metastasis in patients with breast cancer.