Neuropilin 1 and neuropilin 2 co‐expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma

Abstract

BACKGROUND Cell‐retained isoforms of vascular endothelial growth factor A (VEGF‐A) have been reported to play an essential role in tumor progression through stromal neovascularization in malignant solid tumors. While more than 95% of nonsmall cell lung carcinoma (NSCLC) expresses cell‐retained VEGF‐A isoform, the clinicopathologic implications of neuropilin (NRP), considered the specific receptor for limited types of VEGF‐A isoform, are not well understood. METHODS The authors examined NRP1 and NRP2 mRNA expression in 68 NSCLCs and 15 extraneoplastic tissues by a densitometry–assisted, semi‐quantitative reverse transcription‐polymerase chain reaction. The authors determined the distinct expression of NRPs using the expression level of NRPs relative by optical density to β2‐microglobulin. The authors also investigated VEGF‐A isoforms, their receptors, and the clinical implications. Vascularity of NSCLC was morphologically estimated on sections immunostained with anti‐CD34 antibody. RESULTS Eleven of 15 extraneoplastic specimens showed NRP1 expression (73.3%) and 8 showed NRP2 expression (53.3%). The expression level of NRP1 or NRP2 of neoplasmic tissue was higher than that of extraneoplastic tissues (P < 0.01, Mann‐Whitney U test). Fifty‐five and 44 NSCLCs expressed NRP1 and NRP2, respectively. Forty patients co‐expressing NRP1 and NRP2 showed significantly poorer prognosis and increased vessel counts as compared to those 28 cases without co‐expression (P < 0.05, log‐rank test; P < 0.05, Mann‐Whitney U test). CONCLUSIONS The co‐expression of NRP1 and NRP2 genes is significantly correlated with tumor progression through neovascularization in NSCLC. These results suggest that both NRP1 and NRP2 are key molecules for stromal vascularization by cell‐retained VEGF in NSCLC. Cancer 2002;95:2196–201. © 2002 American Cancer Society. DOI 10.1002/cncr.10936

Autocrine semaphorin 3A signaling promotes glioblastoma dispersal

“…Accumulating evidence suggests that neuropilin-1 is overexpressed in several cancers and its high expression is correlated with poor prognosis (Ding et al, 2000;Kawakami et al, 2002;Roche et al, 2002;Vanveldhuizen et al, 2003;Broholm and Laursen, 2004;Fukahi et al, 2004;Li et al, 2004;Osada et al, 2004;Parikh et Figure 8 Semaphorin3A (Sema3A) expression in human glioblastoma multiformes (GBMs). (a) Immunohistochemical analysis of Sema3A in human GBM tissue.…”

“…The expression of neuropilin-1 has been observed previously in several cancers, including GBMs, and its high expression is correlated with poor prognosis (Kawakami et al, 2002;Osada et al, 2004;Kreuter et al, 2006 Figure 1 Functional proteomic screen identifies neuropilin-1 as a mediator of cancer cell invasion. (a) Overview of the proteomic screen.…”

Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells

“…[8][9][10] The cells (passages [20][21][22][23][24][25][26][27][28][29][30] were grown at 371C in a humidified 5% CO 2 atmosphere, and split at a 1:10 ratio, once a week. After growth to a subconfluent state, cells were washed once, made quiescent by incubation in serum-and supplementfree medium for 48 h, and then used for experiments.…”

“…29 Co-expression of NRP1 and NRP2 also increased in the progression from dysplasia to microinvasive lung carcinoma, and correlated significantly with tumor progression and poor prognosis in patients with nonsmall-cell lung carcinoma. 30 Although most studies have indicated a pro-tumorigenic role of NRPs, some reports suggest that NRP1 has a more complex role in some tumor types. NRP1 overexpression in Panc-1 cells was found to reduce tumor volume and incidence, 31 and there is also evidence pointing to potentially differential or antagonistic roles of NRP1 and NRP2 in tumor cell regulation.…”

Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network

“…However, BC cells/tissues as well as other malignancies express various amounts of other VEGF receptors, neuropilins‐1/2 19, 20, 21, 22. One neuropilin, NRP1, is a transmembrane protein that consists of a large extracellular domain, one transmembrane domain, and a relatively short cytoplasmic tail.…”