AIMS: Neuropilin-2 is a coreceptor for vascular endothelial growth factor family members. Blockade of neuropilin-2 is able to suppress lymphogenous metastasis in preclinical models. The aim of this study was to validate a protocol for the evaluation of neuropilin-2 protein expression in situ, by comparison with in-situ hybridization, western blotting, and mRNA expression levels. METHODS AND RESULTS: Immunohistochemistry was performed on normal human tissues, and whole sections for 79 primary non-small-cell lung carcinomas, 65 primary breast carcinomas, 79 primary colorectal cancers, and 52 metastases. Neuropilin-2 expression was observed in lymphatic and blood vessels from all normal and malignant tissues examined. In addition, 32% of primary non-small-cell lung carcinomas, 15% of primary breast carcinomas and 22% of primary colorectal cancers showed tumour cell expression. Fifty-five primary and nine secondary malignant melanomas were also examined for neuropilin-2 expression by in-situ hybridization. All showed vascular expression, and 85% of primary malignant melanomas showed tumour cell expression. CONCLUSIONS: In the majority of lung, breast and colorectal cancers, the effects of anti-neuropilin-2 are likely to be restricted to the vasculature. These results will assist in pharmacokinetic evaluations, tolerability assessments and the choice of setting to evaluate the activity of anti-neuropilin-2 therapies.
AIMS: Neuropilin-2 is a coreceptor for vascular endothelial growth factor family members. Blockade of neuropilin-2 is able to suppress lymphogenous metastasis in preclinical models. The aim of this study was to validate a protocol for the evaluation of neuropilin-2 protein expression in situ, by comparison with in-situ hybridization, western blotting, and mRNA expression levels. METHODS AND RESULTS: Immunohistochemistry was performed on normal human tissues, and whole sections for 79 primary non-small-cell lung carcinomas, 65 primary breast carcinomas, 79 primary colorectal cancers, and 52 metastases. Neuropilin-2 expression was observed in lymphatic and blood vessels from all normal and malignant tissues examined. In addition, 32% of primary non-small-cell lung carcinomas, 15% of primary breast carcinomas and 22% of primary colorectal cancers showed tumour cell expression. Fifty-five primary and nine secondary malignant melanomas were also examined for neuropilin-2 expression by in-situ hybridization. All showed vascular expression, and 85% of primary malignant melanomas showed tumour cell expression. CONCLUSIONS: In the majority of lung, breast and colorectal cancers, the effects of anti-neuropilin-2 are likely to be restricted to the vasculature. These results will assist in pharmacokinetic evaluations, tolerability assessments and the choice of setting to evaluate the activity of anti-neuropilin-2 therapies.
Authors: Aleksandar Boro; Matthias Je Arlt; Harald Lengnick; Bernhard Robl; Maren Husmann; Josefine Bertz; Walter Born; Bruno Fuchs Journal: Am J Transl Res Date: 2015-03-15 Impact factor: 4.060
Authors: Luke H Hoeppner; Steven Bach; Guangqi E; Ying Cao; Yan Guo; Enfeng Wang; Jianmin Wu; Mark J Cowley; David K Chang; Nicola Waddell; Sean M Grimmond; Andrew V Biankin; Roger J Daly; Xiaohui Zhang; Debabrata Mukhopadhyay Journal: Cancer Res Date: 2013-05-20 Impact factor: 12.701
Authors: Bonnie R Joubert; Janine F Felix; Paul Yousefi; Kelly M Bakulski; Allan C Just; Carrie Breton; Sarah E Reese; Christina A Markunas; Rebecca C Richmond; Cheng-Jian Xu; Leanne K Küpers; Sam S Oh; Cathrine Hoyo; Olena Gruzieva; Cilla Söderhäll; Lucas A Salas; Nour Baïz; Hongmei Zhang; Johanna Lepeule; Carlos Ruiz; Symen Ligthart; Tianyuan Wang; Jack A Taylor; Liesbeth Duijts; Gemma C Sharp; Soesma A Jankipersadsing; Roy M Nilsen; Ahmad Vaez; M Daniele Fallin; Donglei Hu; Augusto A Litonjua; Bernard F Fuemmeler; Karen Huen; Juha Kere; Inger Kull; Monica Cheng Munthe-Kaas; Ulrike Gehring; Mariona Bustamante; Marie José Saurel-Coubizolles; Bilal M Quraishi; Jie Ren; Jörg Tost; Juan R Gonzalez; Marjolein J Peters; Siri E Håberg; Zongli Xu; Joyce B van Meurs; Tom R Gaunt; Marjan Kerkhof; Eva Corpeleijn; Andrew P Feinberg; Celeste Eng; Andrea A Baccarelli; Sara E Benjamin Neelon; Asa Bradman; Simon Kebede Merid; Anna Bergström; Zdenko Herceg; Hector Hernandez-Vargas; Bert Brunekreef; Mariona Pinart; Barbara Heude; Susan Ewart; Jin Yao; Nathanaël Lemonnier; Oscar H Franco; Michael C Wu; Albert Hofman; Wendy McArdle; Pieter Van der Vlies; Fahimeh Falahi; Matthew W Gillman; Lisa F Barcellos; Ashish Kumar; Magnus Wickman; Stefano Guerra; Marie-Aline Charles; John Holloway; Charles Auffray; Henning W Tiemeier; George Davey Smith; Dirkje Postma; Marie-France Hivert; Brenda Eskenazi; Martine Vrijheid; Hasan Arshad; Josep M Antó; Abbas Dehghan; Wilfried Karmaus; Isabella Annesi-Maesano; Jordi Sunyer; Akram Ghantous; Göran Pershagen; Nina Holland; Susan K Murphy; Dawn L DeMeo; Esteban G Burchard; Christine Ladd-Acosta; Harold Snieder; Wenche Nystad; Gerard H Koppelman; Caroline L Relton; Vincent W V Jaddoe; Allen Wilcox; Erik Melén; Stephanie J London Journal: Am J Hum Genet Date: 2016-03-31 Impact factor: 11.043