CD147-Cyclophilin a Interactions Promote Proliferation and Survival of Cutaneous T-Cell Lymphoma.

CD147, a transmembrane glycoprotein that belongs to the immunoglobulin superfamily, and cyclophilin A (CypA), one of the binding partners of CD147, are overexpressed in tumor cells and associated with the progression of several malignancies, including both solid and hematological malignancies. However, CD147 and CypA involvement in cutaneous T-cell lymphoma (CTCL) has not been reported. In this study, we examined CD147 and CypA expression and function using clinical samples of mycosis fungoides (MF) and Sézary syndrome (SS) and CTCL cell lines. CD147 and CypA were overexpressed by tumor cells of MF/SS, and CypA was also expressed by epidermal keratinocytes in MF/SS lesional skin. Serum CypA levels were increased and correlated with disease severity markers in MF/SS patients. Anti-CD147 antibody and/or anti-CypA antibody suppressed the proliferation of CTCL cell lines, both in vitro and in vivo, via downregulation of phosphorylated extracellular-regulated kinase 1/2 and Akt. These results suggest that CD147-CypA interactions can contribute to the proliferation of MF/SS tumor cells in both a autocrine and paracrine manner, and that the disruption of CD147-CypA interactions could be a new therapeutic strategy for the treatment of MF/SS.

Serum vascular endothelial growth factor A levels reflect itch severity in mycosis fungoides and Sézary syndrome.

Angiogenesis is an important step to support progression of malignancies, including mycosis fungoides (MF) and Sézary syndrome (SS). Vascular endothelial growth factor (VEGF)-A, a key player in angiogenesis, is secreted by tumor cells of MF/SS and its expression levels in lesional skin correlated with disease severity. In this study, we examined serum VEGF-A levels in MF/SS patients. Serum VEGF-A levels were elevated in patients with erythrodermic MF/SS and the levels decreased after treatment. Importantly, serum VEGF-A levels positively correlated with markers for pruritus. We also found that VEGF-A upregulated mRNA expression of thymic stromal lymphopoietin by keratinocytes. Taken together, our study suggests that VEGF-A can promote progression and pruritus in MF/SS. Inhibition of VEGF-A signaling can be a therapeutic strategy for patients with erythrodermic MF/SS.

Topology Effect of AIEgen-Appended Poly(acrylic acid) with Biocompatible Segments on Ca2+-Sensing and Protein-Adsorption-Resistance Properties.

We recently reported that tetraphenylethene-appended poly(acrylic acid) derivatives (e.g., PAA-TPE0.02) can serve as fluorescent Ca2+ sensors in the presence of physiological concentrations of biologically relevant ions, amino acids, and sugars. However, in the presence of basic proteins such as albumins, the Ca2+-sensing property of the polymer is significantly impaired due to the nonspecific adsorption of protein molecules, which competes with binding to Ca2+. To solve this problem, we explored new designs by focusing on the polymer-chain topology of PAA-TPE0.02 with biocompatible segments. Here, we report the Ca2+-sensing and protein-adsorption-resistance properties of various types of PAA-TPE0.02 copolymers with a poly(oligoethylene glycol acrylate) (polyOEGA) segment, featuring a random, diblock, triblock, or 4-armed-star-block structure. Through this study, we show an interesting topology effect; i.e., a branch-shaped PAA-TPE0.02-co-polyOEGA with biocompatible segments at every terminal (i.e., 4-armed-star-block copolymer) exhibits both good Ca2+-sensing and protein-adsorption-resistance properties.