sVEGFR3 but Not VEGF-C Plasma Level Is Increased in Non-Hodgkin Lymphoma.

BACKGROUND: Non-Hodgkin’s lymphomas (nHL) may spread via blood vasculature or lymphatics. Vascular endothelial growth factor (VEGFs) family of glycoproteins is essential for angiogenesis and lymphangiogenesis. VEGF-C enhances lymphangiogenesis and promotes metastasis via lymphatic vessels. VEGF-C stimulates lymphangiogenesis by binding VEGFR-2 and VEGFR-3 receptors on lymphatic endothelial cells Elevated serum levels of proangiogenic cytokines (i.e. VEGF) are the independent prognostic factor in nHL. Data concerning the role of lymphangiogenesis in nHL are very limited. Salven et al. showed low VEGF -C mRNA in lymphoma cells. The role of lymphangiogenesis in lymphoma dissemination remains to be determined. The aim of the study was to assess plasma levels of VEGF-C and sVEGFR3 in nHL patients. before chemotherapy and after achieving complete remission (CR).

MATERIAL AND METHODS: Plasma samples from 39 adult (18 females and 21 males) patients with B-cell nHL taken at diagnosis and in CR were measured by ELISA to evaluate VEGF-C and sVEGFR-3 levels (Bender Medsystems and R&D Systems respectively). In addition plasma samples from 25 healthy volunteers were evaluated as the control. Statistical analysis was performed using U Mann-Whitney test (p<0,05).

RESULTS: There was no significant differences in VEGF-C levels between untreated nHL group, nHL in CR and the control (166,9±221,8 vs 217±294,4 vs 161,2±118 pg/ml respectively). In untreated nHL patients sVEGFR3 level was significantly higher than in the control (19434±8990 vs 13949±5417 pg/ml respectively; p=0,007). In CR sVEGFR3 decreased but was still significantly higher than in healthy control (18163±9108 vs 13949±5417 pg/ml respectively; p=0,038).

CONCLUSION: Similarly to previous studies we demonstrated that VEGF-C plasma levels were not increased in nHL. There are several observation that in human tumors VEGFR3 is involved both in lymphangiogenesis and angiogenesis. Increased VEGFR3 in nHL may reflect intensity of blood and lymphatic endothelium proliferation.