A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis.

Leukemia inhibitory factor (LIF) is a member of IL-6 family, which serves as a potent chemoattractant for neutrophils as well as a potent angiostatic factor. LIF has been implicated in various autoimmune inflammatory diseases, but its role still remains elusive in systemic sclerosis (SSc). Therefore, we investigated the potential role of LIF in the development of SSc by evaluating the clinical correlation of serum LIF levels, the expression of LIF and its receptors in skin samples, and in vitro experiments with human dermal microvascular endothelial cells. Serum LIF levels were significantly decreased in patients with SSc, especially in those with disease duration of < 1 year compared with healthy controls. As for clinical correlation, SSc patients with digital ulcers exhibited serum LIF levels significantly lower than those without. In immunohistochemistry, the expression of LIF and its receptors, LIF receptor and gp130, was remarkably decreased in dermal blood vessels of SSc lesional skin relative to those of healthy control skin. Furthermore, gene silencing of transcription factor Fli1, whose deficiency is involved in the development of SSc vasculopathy, suppressed the expression of LIF, LIF receptor, and gp130 and Fli1 bound to the promoters of those genes in human dermal microvascular endothelial cells. Collectively, these results suggest that decreased serum LIF levels may be associated with vasculopathy in SSc and that Fli1 deficiency may contribute to the inhibition of LIF-dependent biological effects on SSc endothelial cells by suppressing the expression of LIF, LIF receptor, and gp130.

Glycosylation Changes in Serum Proteins Identify Patients with Pancreatic Cancer.

After more than a decade of biomarker discovery using advanced proteomic and genomic approaches, very few biomarkers have been involved in clinical diagnostics. Most candidate biomarkers are focused on the protein component. Targeting post-translational modifications (PTMs) in combination with protein sequences will provide superior diagnostic information with regards to sensitivity and specificity. Glycosylation is one of the most common and functionally important PTMs. It plays a central role in many biological processes, including protein folding, host-pathogen interactions, immune response, and inflammation. Cancer-associated aberrant glycosylation has been identified in various types of cancer. Expression of cancer-specific glycan epitopes represents an excellent opportunity for diagnostics and potentially specific detection of tumors. Here, we report four proteins (LIFR, CE350, VP13A, HPT) found in sera from pancreatic cancer patients carrying aberrant glycan structures as compared to those of controls.