YKL-40 Promotes Proliferation of Cutaneous T-Cell Lymphoma Tumor Cells through Extracellular Signal-Regulated Kinase Pathways.

YKL-40, one of the chitinase-like proteins, is associated with the pathogenesis of a wide variety of human diseases through modulation of inflammation and tissue remodeling by its diverse roles in cell proliferation, differentiation, and survival. Emerging evidence shows that aberrantly expressed YKL-40 promotes the development of malignancies by inducing proliferation of tumor cells, cytokine production, and angiogenesis by acting on various stromal cells, immune cells, and tumor cells. In this study, we investigated the expression and function of YKL-40 in cutaneous T-cell lymphoma (CTCL). We first revealed that serum YKL-40 levels were increased in patients with CTCL and correlated with disease severity markers. We also found that YKL-40 was expressed by epidermal keratinocytes and tumor cells in lesional skin of CTCL by immunohistochemistry. Although YKL-40 did not affect cytokine production from CTCL cell lines, YKL-40 promoted the proliferation of Hut78 cells and HH cells in vitro, which was dependent on extracellular signal-regulated kinase 1/2 pathways. Moreover, exogenous YKL-40 administration enhanced tumor growth of HH cells in vivo. Our study has suggested that YKL-40 produced from epidermal keratinocytes and CTCL cells promoted the proliferation of CTCL cells through extracellular signal-regulated kinase 1/2 pathways in autocrine and paracrine manners, leading to development of CTCL.

Serum amyloid A levels in the blood of patients with atopic dermatitis and cutaneous T-cell lymphoma.

Serum amyloid A (SAA) is an acute phase protein, which activates immune cells and induces cytokines and chemokine. SAA levels in blood have been reported to be elevated in case of inflammation, infections, neoplasia and tissue injury. In this study, we examined SAA levels in the blood of patients with atopic dermatitis (AD) and cutaneous T-cell lymphoma (CTCL). SAA levels in sera of AD patients, those of CTCL patients and those of healthy controls were not significantly different. When AD or CTCL patients were classified by disease severity, there was still no difference in SAA levels. In AD patients, however, SAA levels positively correlated with the number of eosinophils in peripheral blood and serum soluble interleukin-2 receptor (sIL-2R) levels. There were significant correlations between SAA levels in blood and the number of white blood cells in peripheral blood and serum sIL-2R levels in CTCL patients. AD patients without topical steroid treatment and CTCL patients without narrowband ultraviolet B therapy showed increased levels of SAA, which suggested that SAA levels may easily fluctuate with treatment. These results imply a possible contribution of SAA in development of AD and CTCL.

Increased endocan expression in lesional skin and decreased endocan expression in sera in atopic dermatitis.

Endocan is a novel human endothelial cell-specific molecule and is mainly expressed in endothelial cells in various tissues. Endocan has the capacity to inhibit leukocytes binding to the vascular endothelium. It also can promote the angiogenesis alongside vascular endothelial growth factor A. Through these functions, endocan has been implicated in the pathogenesis of various inflammatory diseases. To investigate the possible roles of endocan in atopic dermatitis (AD), we examined endocan expression in lesional skin and sera in patients with AD. Endocan mRNA and protein levels were increased in lesional skin of AD compared with healthy skin and endocan was expressed on epidermal keratinocytes and dermal endothelial cells. On the other hand, serum endocan levels in patients with AD were significantly lower than those in healthy controls. Our results suggest that elevated endocan expression in lesional skin may be associated with development of AD through angiogenesis and that decreased endocan expression in sera may be associated with increased leukocyte recruitment in AD.