title: The VEGF receptor, neuropilin-1, represents a promising novel target for chronic lymphocytic leukemia patients.
abstract: 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.
authors: Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland.
authors: Agnieszka
authors: A
authors: Piechnik
authors: Anna
authors: A
authors: Dmoszynska
authors: Marcin
authors: M
authors: Omiotek
authors: Radosław
authors: R
authors: Mlak
authors: Małgorzata
authors: M
authors: Kowal
authors: Stephan
authors: S
authors: Stilgenbauer
authors: Lars
authors: L
authors: Bullinger
authors: Krzysztof
authors: K
authors: Giannopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003713:Dendritic Cells / Q000737:chemistry; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology*; D039942:Neuropilin-1 / Q000032:analysis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry; D013792:Thalidomide / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics / Q000502:physiology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D013792:Thalidomide
keywords: chronic lymphocytic leukemia; neuropilin-1; vascular endothelial growth factor