Angiogenin levels are increased in lesional skin and sera in patients with erythrodermic cutaneous T cell lymphoma

Abstract

Angiogenin is a member of the ribonuclease superfamily that is associated with the angiogenic process. Angiogenesis is regarded as an important step to support primary and metastatic tumor growth. In cutaneous T cell lymphoma (CTCL), angiogenesis in lesional skin is increased, suggesting that interaction between tumor cells and their microvasculature are likely to occur during progression of CTCL. Patients with hematological malignancies show increased serum angiogenin levels, which are related with poor overall survival. To investigate possible roles of angiogenin in development of CTCL, we measured serum angiogenin levels in 36 patients with CTCL and 21 healthy controls by enzyme-linked immunosorbent assay. We also investigated angiogenin mRNA and protein expression in lesional skin of CTCL by quantitative RT-PCR and immunohistochemistry. Serum angiogenin levels in patients with CTCL were significantly higher than those in healthy controls. When classified with types of skin lesions, serum angiogenin levels were elevated only in erythrodermic CTCL patients. Angiogenin mRNA expression levels in lesional skin were significantly elevated in erythrodermic CTCL compared to normal skin. Immunohistochemical study revealed that angiogenin was expressed by keratinocytes, endothelial cells, and infiltrating lymphocytes in CTCL. Our results suggest that enhanced angiogenin expression may be related with a poor prognosis of erythrodermic CTCL. As angiogenin acts as an inhibitor of polymorphonuclear leukocyte degranulation, angiogenin may also be linked to impaired host defense in erythrodermic CTCL.

Placental Growth Factor and Vascular Endothelial Growth Factor Together Regulate Tumour Progression via Increased Vasculature in Cutaneous T-cell Lymphoma

“…Similarly, in CTCL, angiogenesis, assessed either by microvessel density or by microvessel number in lesional skin, is increased, suggesting that interaction between tumour cells and their microvasculature is likely to occur during the progression of CTCL (8,9). Consistent with those reports, increased expression of angiogenin, one of the angiogenic factors, in the sera and lesional skin was reported in patients with erythrodermic CTCL (10). Serum levels of angiopoietin-2 (Ang-2), which has the capacity to promote both angiogenesis and lymphangiogenesis, are also elevated in patients with SS and are correlated with disease severity markers (11).…”

Angiogenin expression in the sera and skin of patients with rheumatic diseases

“…It was reported that serum angiogenin levels increase in patients with cutaneous T cell lymphoma, and the molecule is thought to act as an inhibitor of polymorphonuclear leukocyte degranulation (20). Elevated levels of angiogenin have also been detected in the sera of patients with pancreatic cancer and from 5 DM patients, 4 CADM patients and 5 SLE patients, mean relative transcript levels of angiogenin in skin tissues from DM/CADM patients were significantly up-regulated compared with the values in normal skin (p = 0.007 and 0.014, respectively) and SLE skin (p = 0.009 and 0.014, respectively) ( Figure 2).…”

Immunological milieu in mycosis fungoides and Sézary syndrome

“…Tumor cells of MF or SS expressed vascular endothelial growth factor (VEGF), which plays a central role in tumor‐associated angiogenesis, through Janus kinase 3 and the c‐Jun N‐terminal kinase‐dependent signal pathways . Expression of angiogenin, which is a member of the ribonuclease superfamily that is associated with the angiogenic process, was also elevated in lesional skin of erythrodermic MF or SS . The main sources of angiogenin were keratinocytes, endothelial cells and infiltrating T cells .…”

“…Expression of angiogenin, which is a member of the ribonuclease superfamily that is associated with the angiogenic process, was also elevated in lesional skin of erythrodermic MF or SS . The main sources of angiogenin were keratinocytes, endothelial cells and infiltrating T cells . Angiopoietin‐2 (Ang‐2) is one of the ligands for the endothelium‐specific tyrosine kinase Tie2 receptor and involved in angiogenesis alongside VEGF .…”

“…111 The main sources of angiogenin were keratinocytes, endothelial cells and infiltrating T cells. 111 Angiopoietin-2 (Ang-2) is one of the ligands for the endothelium-specific tyrosine kinase Tie2 receptor and involved in angiogenesis alongside VEGF. 112,113 In lesional skin of CTCL, Ang-2 was expressed by endothelial cells and tumor cells, and the numbers of Ang-2-positive cells were correlated with those of microvessels.…”