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The VEGF receptor, neuropilin‐1, represents a promising novel target for chronic lymphocytic leukemia patients
Author(s) -
Piechnik Agnieszka,
Dmoszynska Anna,
Omiotek Marcin,
Mlak Radosław,
Kowal Małgorzata,
Stilgenbauer Stephan,
Bullinger Lars,
Giannopoulos Krzysztof
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28135
Subject(s) - chronic lymphocytic leukemia , neuropilin 1 , vegf receptors , medicine , leukemia , receptor , cancer research , immunology , vascular endothelial growth factor
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 < 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 < 0.0001 and r 2 = 0.49, p < 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.