{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:38:36Z","timestamp":1790473116172,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s12964-019-0368-9","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T12:02:53Z","timestamp":1560772973000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Neuropilin-1 drives tumor-specific uptake of chlorotoxin"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8066-0575","authenticated-orcid":false,"given":"Sharon","family":"McGonigle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utpal","family":"Majumder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Kolber-Simonds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Noland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"TenDyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Custar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten H. D.","family":"Postema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. George","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie C.","family":"Twine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Woodall-Jappe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Nomoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,17]]},"reference":[{"issue":"2 Pt 1","key":"368_CR1","doi-asserted-by":"publisher","first-page":"C361","DOI":"10.1152\/ajpcell.1993.264.2.C361","volume":"264","author":"JA DeBin","year":"1993","unstructured":"DeBin JA, Maggio JE, Strichartz GR. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am J Phys. 1993;264(2 Pt 1):C361\u20139.","journal-title":"Am J Phys"},{"issue":"21","key":"368_CR2","first-page":"4871","volume":"58","author":"L Soroceanu","year":"1998","unstructured":"Soroceanu L, Gillespie Y, Khazaeli MB, Sontheimer H. Use of chlorotoxin for targeting of primary brain tumors. Cancer Res. 1998;58(21):4871\u20139.","journal-title":"Cancer Res"},{"issue":"22","key":"368_CR3","doi-asserted-by":"publisher","first-page":"3644","DOI":"10.1200\/JCO.2005.05.4569","volume":"24","author":"AN Mamelak","year":"2006","unstructured":"Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, et al. Phase I single-dose study of Intracavitary-administered Iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol. 2006;24(22):3644\u201350.","journal-title":"J Clin Oncol"},{"key":"368_CR4","doi-asserted-by":"publisher","first-page":"no.15S","DOI":"10.1200\/jco.2009.27.15s.e14507","volume":"27","author":"TE Gribbin","year":"2009","unstructured":"Gribbin TE, Senzer N, Raizer JJ, Shen S, Nabors LB, Wiranowska M, et al. A phase I evaluation of intravenous (IV) 131I-chlorotoxin delivery to solid peripheral and intracranial tumors. J Clin Oncol. 2009;27:no.15S. \n                    https:\/\/doi.org\/10.1200\/jco.2009.27.15s.e14507\n                    \n                  .","journal-title":"J Clin Oncol"},{"issue":"2","key":"368_CR5","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.3171\/2013.11.FOCUS13497","volume":"36","author":"PV Butte","year":"2014","unstructured":"Butte PV, Mamelak A, Parrish-Novak J, Drazin D, Shweikeh F, Gangalum PR, et al. Near-infrared imaging of brain tumors using the tumor paint BLZ-100 to achieve near-complete resection of brain tumors. Neurosurg Focus. 2014;36(2):E1. \n                    https:\/\/doi.org\/10.3171\/2013.11.FOCUS13497\n                    \n                  .","journal-title":"Neurosurg Focus"},{"key":"368_CR6","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1002\/glia.10083","volume":"39","author":"SA Lyons","year":"2002","unstructured":"Lyons SA, O\u2019Neal J, Sontheimer H. Chlorotoxin, a scorpion derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia. 2002;39:162\u201373.","journal-title":"Glia"},{"issue":"14","key":"368_CR7","doi-asserted-by":"publisher","first-page":"5942","DOI":"10.1523\/JNEUROSCI.19-14-05942.1999","volume":"19","author":"L Soroceanu","year":"1999","unstructured":"Soroceanu L, Manning TJ Jr, Sontheimer H. Modulation of glioma cell migration and invasion using cl\u2212 and K+ ion channel blockers. J Neurosci. 1999;19(14):5942\u201354.","journal-title":"J Neurosci"},{"issue":"6","key":"368_CR8","doi-asserted-by":"publisher","first-page":"4135","DOI":"10.1074\/jbc.M205662200","volume":"278","author":"J Deshane","year":"2003","unstructured":"Deshane J, Garner CC, Sontheimer H. Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2. J Biol Chem. 2003;278(6):4135\u201344.","journal-title":"J Biol Chem"},{"issue":"1","key":"368_CR9","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1017\/S1740925X06000044","volume":"2","author":"MB McFerrin","year":"2006","unstructured":"McFerrin MB, Sontheimer H. A role for ion channels in glioma cell invasion. Neuron Glia Biol. 2006;2(1):39\u201349.","journal-title":"Neuron Glia Biol"},{"key":"368_CR10","doi-asserted-by":"publisher","first-page":"6882","DOI":"10.1158\/0008-5472.CAN-06-3948","volume":"67","author":"M Veiseh","year":"2007","unstructured":"Veiseh M, Gabikian P, Bahrami S-B, Veiseh O, Zhang M, Hackman RC, et al. Tumor paint: a Chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of Cancer foci. Cancer Res. 2007;67:6882\u20138.","journal-title":"Cancer Res"},{"issue":"7","key":"368_CR11","doi-asserted-by":"publisher","first-page":"4366","DOI":"10.1074\/jbc.M109.066092","volume":"285","author":"K Kesavan","year":"2010","unstructured":"Kesavan K, Ratliff J, Johnson EW, Dahlberg W, Asara JM, Misra P, et al. Annexin A2 is a molecular target for TM601, a peptide with tumor-targeting and anti-angiogenic effects. J Biol Chem. 2010;285(7):4366\u201374. \n                    https:\/\/doi.org\/10.1074\/jbc.M109.066092\n                    \n                  .","journal-title":"J Biol Chem"},{"issue":"1","key":"368_CR12","first-page":"39","volume":"30","author":"DB Jacoby","year":"2010","unstructured":"Jacoby DB, Dyskin E, Yalcin M, Kesevan K, Dahlberg W, Ratliff J, et al. Potent pleiotropic anti-angiogenic effects of TM601, a synthetic chlorotoxin peptide. Anticancer Res. 2010;30(1):39\u201346.","journal-title":"Anticancer Res"},{"issue":"3","key":"368_CR13","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1002\/jcp.22296","volume":"225","author":"R Lima e Silva","year":"2010","unstructured":"Lima e Silva R, Shen J, Gong YY, Seidel CP, Hackett SF, Kesavan K, et al. Agents that bind annexin A2 suppress ocular neovascularization. J Cell Physiol. 2010;225(3):855\u201364. \n                    https:\/\/doi.org\/10.1002\/jcp.22296\n                    \n                  .","journal-title":"J Cell Physiol"},{"key":"368_CR14","unstructured":"McGonigle S, Majumder U, Custar DW, Wu J, Postema MHD. Peptide Drug Conjugates. WO 2017\/136769; 2017. Retrieved from \n                    https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2017136769&recNum=46&docAn=US2017016575&queryString=EN_ALL:nmr%20AND%20PA:(eisai)&maxRec=1987\n                    \n                  ."},{"issue":"38","key":"368_CR15","doi-asserted-by":"publisher","first-page":"16157","DOI":"10.1073\/pnas.0908201106","volume":"106","author":"T Teesalu","year":"2009","unstructured":"Teesalu T, Sugahara KN, Kotamraju VR, Ruoslahti E. C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. PNAS. 2009;106(38):16157\u201362. \n                    https:\/\/doi.org\/10.1073\/pnas.0908201106\n                    \n                  .","journal-title":"PNAS"},{"issue":"5981","key":"368_CR16","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1126\/science.1183057","volume":"328","author":"KN Sugahara","year":"2010","unstructured":"Sugahara KN, Teesalu T, Karmali PP, Kotamraju VR, Agemy L, Greenwald DR, et al. Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science. 2010;328(5981):1031\u20135. \n                    https:\/\/doi.org\/10.1126\/science.1183057\n                    \n                  .","journal-title":"Science"},{"key":"368_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7240","volume":"6","author":"HB Wang","year":"2015","unstructured":"Wang HB, Zhang H, Zhang J-P, Li Y, Zhao B, Feng G-K, et al. Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells. Nat Commun. 2015;6:6240. \n                    https:\/\/doi.org\/10.1038\/ncomms7240\n                    \n                  .","journal-title":"Nat Commun"},{"issue":"24","key":"368_CR18","doi-asserted-by":"publisher","first-page":"10295","DOI":"10.1074\/jbc.M116.773051","volume":"292","author":"C Kerros","year":"2017","unstructured":"Kerros C, Tripathi SC, Zha D, Mehrens JM, Sergeeva A, Philips AV, et al. Neuropilin-1 mediates neutrophil elastase uptake and cross-presentation in breast cancer cells. J Biol Chem. 2017;292(24):10295\u2013305. \n                    https:\/\/doi.org\/10.1074\/jbc.M116.773051\n                    \n                  .","journal-title":"J Biol Chem"},{"key":"368_CR19","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jocn.2016.04.012","volume":"33","author":"O Cohen-Inbar","year":"2016","unstructured":"Cohen-Inbar O, Zaaroor M. Glioblastoma multiforme targeted therapy: the chlorotoxin story. J Clin Neurosci. 2016;33:52\u20138. \n                    https:\/\/doi.org\/10.1016\/j.jocn.2016.04.012\n                    \n                  .","journal-title":"J Clin Neurosci"},{"issue":"7","key":"368_CR20","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1016\/j.nano.2016.03.005","volume":"12","author":"L Han","year":"2016","unstructured":"Han L, Cai Q, Tian D, Kong DK, Gou X, Chen Z, et al. Targeted drug delivery to ischemic stroke via chlorotoxin-anchored, lexiscan-loaded nanoparticles. Nanomedicine. 2016;12(7):1833\u201342. \n                    https:\/\/doi.org\/10.1016\/j.nano.2016.03.005\n                    \n                  .","journal-title":"Nanomedicine"},{"issue":"3","key":"368_CR21","doi-asserted-by":"publisher","first-page":"659","DOI":"10.3390\/ijms19030659","volume":"19","author":"H Mahmud","year":"2018","unstructured":"Mahmud H, Kasai T, Khayrani AC, Asakura M, Oo AKK, Du J, et al. Targeting glioblastoma cells expressing CD44 with liposomes encapsulating doxorubicin and displaying Chlorotoxin-IgG fc fusion protein. Int J Mol Sci. 2018;19(3):659. \n                    https:\/\/doi.org\/10.3390\/ijms19030659\n                    \n                  .","journal-title":"Int J Mol Sci"},{"issue":"10","key":"368_CR22","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1016\/j.bbamcr.2017.06.012","volume":"1864","author":"F Beaumatin","year":"2017","unstructured":"Beaumatin F, El Dhaybi M, Bobo C, Verdier M, Priault M. Bcl-xL deamidation and cancer: charting the fame trajectories of legitimate child and hidden siblings. Biochim Biophys Acta. 2017;1864(10):1734\u201345. \n                    https:\/\/doi.org\/10.1016\/j.bbamcr.2017.06.012\n                    \n                  .","journal-title":"Biochim Biophys Acta"},{"issue":"49","key":"368_CR23","doi-asserted-by":"publisher","first-page":"29120","DOI":"10.1074\/jbc.R115.687327","volume":"290","author":"HF Guo","year":"2015","unstructured":"Guo HF, Vander Kooi CW. Neuropilin functions as an essential cell surface receptor. J Biol Chem. 2015;290(49):29120\u20136. \n                    https:\/\/doi.org\/10.1074\/jbc.R115.687327\n                    \n                  .","journal-title":"J Biol Chem"},{"issue":"9","key":"368_CR24","doi-asserted-by":"crossref","first-page":"921","DOI":"10.18632\/oncotarget.626","volume":"3","author":"GJ Prud\u2019homme","year":"2012","unstructured":"Prud\u2019homme GJ, Glinka Y. Neuropilins are multifunctional coreceptors involved in tumor initiation, growth, metastasis and immunity. Oncotarget. 2012;3(9):921\u201339.","journal-title":"Oncotarget"},{"issue":"7","key":"368_CR25","first-page":"13942","volume":"9","author":"H Zhang","year":"2016","unstructured":"Zhang H, He C, Han S, Zhu M, Ke W. The prognostic value of neuropilin-1 in various cancers: a meta-analysis. Int J Clin Exp Med. 2016;9(7):13942\u20139.","journal-title":"Int J Clin Exp Med"},{"key":"368_CR26","doi-asserted-by":"publisher","first-page":"4904","DOI":"10.1038\/ncomms5904","volume":"5","author":"H-B Pang","year":"2014","unstructured":"Pang H-B, Braun GB, Friman T, Aza-Blanc P, Ruidiaz ME, Sugahara KN, et al. An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability. Nat Commun. 2014;5:4904. \n                    https:\/\/doi.org\/10.1038\/ncomms5904\n                    \n                  .","journal-title":"Nat Commun"},{"issue":"14","key":"368_CR27","doi-asserted-by":"publisher","first-page":"6844","DOI":"10.1128\/JVI.02719-05","volume":"80","author":"D Ghez","year":"2006","unstructured":"Ghez D, Lepelletier Y, Lambert S, Fourneau JM, Blot V, Janvier S, et al. Neuropilin-1 is involved in human T-cell Lymphotropic virus type 1 entry. J Virol. 2006;80(14):6844\u201354. \n                    https:\/\/doi.org\/10.1128\/JVI.02719-05\n                    \n                  .","journal-title":"J Virol"},{"issue":"42","key":"368_CR28","doi-asserted-by":"publisher","first-page":"68057","DOI":"10.18632\/oncotarget.10929","volume":"7","author":"GJ Prud\u2019homme","year":"2017","unstructured":"Prud\u2019homme GJ, Glinka Y, Lichner Z, Yousef GM. Neuropilin-1 is a receptor for extracellular miRNA and AGO2\/ miRNA complexes and mediates the internalization of miRNAs that modulate cell function. Oncotarget. 2017;7(42):68057\u201371. \n                    https:\/\/doi.org\/10.18632\/oncotarget.10929\n                    \n                  .","journal-title":"Oncotarget"},{"key":"368_CR29","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s10637-014-0071-z","volume":"32","author":"CD Weekes","year":"2014","unstructured":"Weekes CD, Beeram M, Tolcher AW, Papadopoulos KP, Gore L, Hegde P, et al. A phase I study of the human monocloncal anti-NRP1 antibody MNRP1685A in patients with advanced solid tumors. Investig New Drugs. 2014;32:653\u201360.","journal-title":"Investig New Drugs"},{"key":"368_CR30","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1007\/s00280-014-2426-8","volume":"73","author":"A Patnaik","year":"2014","unstructured":"Patnaik A, LoRusso PM, Messersmith WA, Papadopoulos KP, Gore L, Beeram M, et al. Phase Ib study evaluating MNRP1685A, a fully human anti-NRP1 monoclonal antibody, in combination with bevacizumab and paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014;73:951\u201360. \n                    https:\/\/doi.org\/10.1007\/s00280-014-2426-8\n                    \n                  .","journal-title":"Cancer Chemother Pharmacol"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-019-0368-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12964-019-0368-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-019-0368-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T23:19:42Z","timestamp":1592263182000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-019-0368-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,17]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["368"],"URL":"https:\/\/doi.org\/10.1186\/s12964-019-0368-9","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,17]]},"assertion":[{"value":"7 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All studies were performed according to IACUC approved protocols.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"67"}}