The VEGF receptor, neuropilin-1, represents a promising novel target for chronic lymphocytic leukemia patients

作者：Piechnik Agnieszka; Dmoszynska Anna; Omiotek Marcin; Mlak Radoslaw; Kowal Malgorzata; Stilgenbauer Stephan; Bullinger Lars; Giannopoulos Krzysztof^*

来源：International Journal of Cancer, 2013, 133(6): 1489-1496.

DOI：10.1002/ijc.28135

• chronic lymphocytic leukemia
• vascular endothelial growth factor
• neuropilin-1

Angiogenesis has been shown to substantially contribute to the progression of chronic lymphocytic leukemia (CLL). Neuropilin-1 (NRP1) represents a receptor for vascular endothelial growth factor (VEGF), which has been reported to be overexpressed in several malignancies. In our study, we characterized mRNA levels of VEGF receptors including NRP1 in a large cohort of CLL patients (n=114), additionally we performed a detailed characterization of NRP1 expression on B cells, plasmacytoid dendritic cells (PDCs) and regulatory T cells (Tregs). The expression of NRP1 was significantly higher on leukemic lymphocytes compared to control B lymphocytes on mRNA and protein levels (22.72% vs. 0.2%, p=0.0003, respectively), Tregs (42.6% vs. 16.05%, p=0.0003) and PDCs (100% vs. 98% p%26lt;0.0001). In functional studies, we found higher NRP1 expression on CLL cells after stimulation with VEGF. The correlation between expression of VEGF receptors: FLT1, NRP1 and FOXP3 expression (r(2)=0.53, p%26lt;0.0001 and r(2)=0.49, p%26lt;0.0001, respectively) was observed. Earlier we described the specific Treg reduction during the therapy with thalidomide in vivo. Now we observe the reduction of the NRP1 expression on Tregs in vitro, thereby suggesting a possible target of thalidomide action. In conclusion, NRP1 might represent an interesting link between angiogenesis and tolerance mechanisms and represents interesting target for therapy. %26lt;br%26gt;What%26apos;s new? The VEGF receptor neuropilin-1 (NRP1) may be a critical link between angiogenesis and immune tolerance in chronic lymphocytic leukemia (CLL). Here, NRP1 expression and functional significance in CLL are characterized in detail. The work reveals significant elevation in the receptor%26apos;s mRNA and protein levels in not only B lymphocytes but also regulatory T cells (Tregs) and plasmacytoid dendritic cells (PDCs), which mediate tumor escape from immunosurveillance. In addition, VEGF stimulation of CLL cells was associated with increased NRP1 expression, suggesting a regulatory role over receptor expression for VEGF in CLL.

• 出版日期2013-9-15