Psoriasin potential target for psoriasis therapy
MedWire News: Research suggests that blocking the formation of psoriasin, a protein that is abundant in the skin of psoriasis patients and thought to play a role in breast cancer progression, may help combat symptoms of the skin condition.
"We want to examine the ability of psoriasin as a target for therapy. By inhibiting psoriasin, we believe we can reduce vascular formation and thus the proliferation of the disease's magnitude and intensity," said study author Charlotta Enerbäck (Linköping University, Sweden) in a press statement.
Psoriasin is a calcium-binding protein that is induced by reactive oxygen species (ROS) and is known to increase expression of vascular endothelial growth factor (VEGF) and promote tumor growth.
In this study, Enerbäck and colleagues assessed the effect of psoriasin on endothelial cells in culture.
They found that recombinant psoriasin acts to increase VEGF expression in mammary epithelial cells and increased the proliferation of endothelial cells to a level comparable to that observed with recombinant VEGF protein.
Of note, when endothelial cells were exposed to psoriasin-expressing adenoviruses, no change in proliferation was seen suggesting that this effect must be mediated by a specific receptor.
Treatment of cells with the soluble form of the receptor for advanced glycation end products (sRAGE), which targets RAGE, led to inhibition of the proliferative effects of psoriasin, suggesting that the protein acts through this receptor.
Psoriasin was also shown to induce formation of ROS, as VEGF expression was not triggered by hydrogen peroxide when psoriasin was silenced. In addition to blocking the proliferative effects of psoriasin, sRAGE also blocked formation of ROS, write Enerbäck et al in Breast Cancer Research and Treatment.
The team says that in addition to its effects on the skin of psoriasis patients, psoriasin may also promote breast cancer progression through induction of the oxidative stress response and angiogenesis.
"Since psoriasin expresses itself specifically only in the diseased psoriatic skin, we expect that inhibitors against this are highly selective and effective against the disease, and that the risk for side effects is minimal," commented Enerbäck.
The team adds that the protein also has potential as a novel anti-angiogenic target in patients with breast cancer.
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By Helen Albert