Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth.

Abstract:

:Neuropilin-1 (NRP1) guides the development of the nervous and vascular systems. Binding to either semaphorins or VEGF, NRP1 acts with plexins to regulate neuronal guidance, or with VEGFR2 to mediate vascular development. We have generated two monoclonal antibodies that bind to the Sema- and VEGF-binding domains of NRP1, respectively. Both antibodies reduce angiogenesis and vascular remodeling, while having little effect on other VEGFR2-mediated events. Importantly, anti-NRP1 antibodies have an additive effect with anti-VEGF therapy in reducing tumor growth. Vessels from tumors treated with anti-VEGF show a close association with pericytes, while tumors treated with both anti-NRP1 and anti-VEGF lack this organization. We propose that blocking NRP1 function inhibits vascular remodeling, rendering vessels more susceptible to anti-VEGF therapy.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Pan Q,Chanthery Y,Liang WC,Stawicki S,Mak J,Rathore N,Tong RK,Kowalski J,Yee SF,Pacheco G,Ross S,Cheng Z,Le Couter J,Plowman G,Peale F,Koch AW,Wu Y,Bagri A,Tessier-Lavigne M,Watts RJ

doi

10.1016/j.ccr.2006.10.018

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

53-67

issue

1

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(06)00367-9

journal_volume

11

pub_type

杂志文章
  • Using small molecules to overcome drug resistance induced by a viral oncogene.

    abstract::We used small molecule screening to discover compounds and mechanisms for overcoming E6 oncogene-mediated drug resistance. Using high-throughput screening in isogenic cell lines, we identified compounds that potentiate doxorubicin's lethality in E6-expressing colon cancer cells. Such compounds included quaternary ammo...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2006.01.012

    authors: Smukste I,Bhalala O,Persico M,Stockwell BR

    更新日期:2006-02-01 00:00:00

  • Neuroblastoma Metastases: Leveraging the Avian Neural Crest.

    abstract::Neuroblastoma, an embryonal cancer of neural crest origin, shows metastases frequently at diagnosis. In this issue of Cancer Cell, Delloye-Bourgeois and colleagues demonstrate that neuroblastoma cell lines and patient-derived xenografts engraft and adopt a metastatic program in chick embryos. They identify Sema3C as a...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2017.09.012

    authors: Zheng T,Ménard M,Weiss WA

    更新日期:2017-10-09 00:00:00

  • Proapoptotic activation of death receptor 5 on tumor endothelial cells disrupts the vasculature and reduces tumor growth.

    abstract::The proapoptotic death receptor DR5 has been studied extensively in cancer cells, but its action in the tumor microenvironment is not well defined. Here, we uncover a role for DR5 signaling in tumor endothelial cells (ECs). We detected DR5 expression in ECs within tumors but not normal tissues. Treatment of tumor-bear...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2012.05.014

    authors: Wilson NS,Yang A,Yang B,Couto S,Stern H,Gogineni A,Pitti R,Marsters S,Weimer RM,Singh M,Ashkenazi A

    更新日期:2012-07-10 00:00:00

  • NAD(+) supplementation as a novel approach to cURIng HCC?

    abstract::In this issue of Cancer Cell, Tummala and colleagues demonstrate that unconventional prefoldin RPB5 interactor (URI) expression in hepatocytes leads to hepatocellular carcinoma (HCC) development by interacting with L-tryptophan/kynurenine/nicotinamide adenine dinucleotide (NAD(+)) metabolism. The results suggest that ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2014.11.011

    authors: Mederacke I,Schwabe RF

    更新日期:2014-12-08 00:00:00

  • Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation.

    abstract::Chronic exposure to tobacco smoke, which contains over 60 tumor-initiating carcinogens, is the major risk factor for development of lung cancer, accounting for a large portion of cancer-related deaths worldwide. It is well established that tobacco smoke is a tumor initiator, but we asked whether it also acts as a tumo...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2009.12.008

    authors: Takahashi H,Ogata H,Nishigaki R,Broide DH,Karin M

    更新日期:2010-01-19 00:00:00

  • EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis.

    abstract::The EZH2 histone methyltransferase mediates the humoral immune response and drives lymphomagenesis through formation of bivalent chromatin domains at critical germinal center (GC) B cell promoters. Herein we show that the actions of EZH2 in driving GC formation and lymphoma precursor lesions require site-specific bind...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2016.07.006

    authors: Béguelin W,Teater M,Gearhart MD,Calvo Fernández MT,Goldstein RL,Cárdenas MG,Hatzi K,Rosen M,Shen H,Corcoran CM,Hamline MY,Gascoyne RD,Levine RL,Abdel-Wahab O,Licht JD,Shaknovich R,Elemento O,Bardwell VJ,Melnick AM

    更新日期:2016-08-08 00:00:00

  • Reinforcing suppression using regulators: a new link between STAT3, IL-23, and Tregs in tumor immunosuppression.

    abstract::STAT3 plays many roles in tumorigenesis. In this issue of Cancer Cell, Kortylewski et al. show that in the tumor microenvironment, STAT3 enhances the expression of the protumor cytokine IL-23 in macrophages but inhibits the antitumor cytokine IL-12 in dendritic cells. STAT3 also mediates IL-23's effect of activating t...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2009.01.008

    authors: Stewart CA,Trinchieri G

    更新日期:2009-02-03 00:00:00

  • The RB and p53 pathways in cancer.

    abstract::The life history of cancer cells encompasses a series of genetic missteps in which normal cells are progressively transformed into tumor cells that invade surrounding tissues and become malignant. Most prominent among the regulators disrupted in cancer cells are two tumor suppressors, the retinoblastoma protein (RB) a...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/s1535-6108(02)00102-2

    authors: Sherr CJ,McCormick F

    更新日期:2002-08-01 00:00:00

  • Successful targeting of ErbB2 receptors-is PTEN the key?

    abstract::Women with ErbB2-positive breast cancer have a poor prognosis, and frequently, chemotherapy treatment is ineffective. The ErbB2-targeted antibody trastuzumab improves survival when given with chemotherapy to patients with ErbB2-overexpressing metastatic disease, but treatment is not curative, and primary resistance is...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2004.08.001

    authors: Crowder RJ,Lombardi DP,Ellis MJ

    更新日期:2004-08-01 00:00:00

  • Impact of COVID-19 Pandemic on Cancer Research.

    abstract::The COVID-19 pandemic is profoundly changing cancer researchers and cancer research. Leaders from different fields and at different career stages share their perspectives. ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2020.10.007

    authors: Zon L,Gomes AP,Cance WG,Ribas A,Tuveson D,Postel-Vinay S,Massard C,Barlési F

    更新日期:2020-11-09 00:00:00

  • Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis.

    abstract::The receptor tyrosine kinase HER2 enhances tumor metastasis; however, its role in homing to metastatic organs is poorly understood. The chemokine receptor CXCR4 has recently been shown to mediate the movement of malignant cancer cells to specific organs. Here, we show that HER2 enhances the expression of CXCR4, which ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2004.09.027

    authors: Li YM,Pan Y,Wei Y,Cheng X,Zhou BP,Tan M,Zhou X,Xia W,Hortobagyi GN,Yu D,Hung MC

    更新日期:2004-11-01 00:00:00

  • ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis.

    abstract::Inhibition of ERK-MAPK signaling by expression of dominant-negative MEK1 in the tumor vasculature suppresses angiogenesis and tumor growth. In an organotypic tissue culture angiogenesis assay, ERK-MAPK inhibition during the migratory phase results in loss of bipolarity, detachment, and cell death of isolated endotheli...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2005.12.021

    authors: Mavria G,Vercoulen Y,Yeo M,Paterson H,Karasarides M,Marais R,Bird D,Marshall CJ

    更新日期:2006-01-01 00:00:00

  • TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma.

    abstract::Glioma-initiating cells (GICs) are responsible for the initiation and recurrence of gliomas. Here, we identify a molecular mechanism that regulates the self-renewal capacity of patient-derived GICs. We show that TGF-beta and LIF induce the self-renewal capacity and prevent the differentiation of GICs. TGF-beta induces...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2009.02.011

    authors: Peñuelas S,Anido J,Prieto-Sánchez RM,Folch G,Barba I,Cuartas I,García-Dorado D,Poca MA,Sahuquillo J,Baselga J,Seoane J

    更新日期:2009-04-07 00:00:00

  • Targeting the Residual Leukemia Cells after Chemotherapy.

    abstract::One of the biggest challenges in treating acute myeloid leukemia (AML) is relapse of aggressive disease after treatment. In this issue of Cancer Cell, Boyd et al. characterize a molecularly distinct population of chemotherapy-induced transient leukemic regenerating cells (LRCs), which can be exploited to prevent AML r...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2018.08.012

    authors: Vu LP,Kharas MG

    更新日期:2018-09-10 00:00:00

  • A new mode of RAF autoregulation: a further complication in the inhibitor paradox.

    abstract::ERK pathway activation in cells expressing wild-type BRAF is a well-reported, clinically-relevant adverse effect of the otherwise impressive response of BRAF(V600E)-mutated melanomas to RAF inhibitors. In this issue of Cancer Cell, Holderfield and colleagues show that RAF autoinhibition underpins this paradox, further...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2013.04.021

    authors: Hey F,Pritchard C

    更新日期:2013-05-13 00:00:00

  • Structural basis for inhibition of the epidermal growth factor receptor by cetuximab.

    abstract::Recent structural studies of epidermal growth factor receptor (EGFR) family extracellular regions have identified an unexpected mechanism for ligand-induced receptor dimerization that has important implications for activation and inhibition of these receptors. Here we describe the 2.8 angstroms resolution X-ray crysta...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2005.03.003

    authors: Li S,Schmitz KR,Jeffrey PD,Wiltzius JJ,Kussie P,Ferguson KM

    更新日期:2005-04-01 00:00:00

  • GEMMs shine a light on resistance to androgen deprivation therapy for prostate cancer.

    abstract::Androgen deprivation therapy (ADT) for advanced prostate cancer inexorably leads to resistance, and clinically useful biomarkers are lacking. The value of genetically engineered mice for coclinical studies is clearly demonstrated in a recent publication that reveals XAF1, XIAP, and SRD5A1 as novel predictive biomarker...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2013.06.007

    authors: Karantanos T,Thompson TC

    更新日期:2013-07-08 00:00:00

  • TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer.

    abstract::The MAP3-kinase TGF-beta-activated kinase 1 (TAK1) critically modulates innate and adaptive immune responses and connects cytokine stimulation with activation of inflammatory signaling pathways. Here, we report that conditional ablation of TAK1 in liver parenchymal cells (hepatocytes and cholangiocytes) causes hepatoc...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2010.03.021

    authors: Bettermann K,Vucur M,Haybaeck J,Koppe C,Janssen J,Heymann F,Weber A,Weiskirchen R,Liedtke C,Gassler N,Müller M,de Vos R,Wolf MJ,Boege Y,Seleznik GM,Zeller N,Erny D,Fuchs T,Zoller S,Cairo S,Buendia MA,Prinz M,A

    更新日期:2010-05-18 00:00:00

  • Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.

    abstract::Through in silico and other analyses, we identified FOXC1 as expressed in at least 20% of human AML cases, but not in normal hematopoietic populations. FOXC1 expression in AML was almost exclusively associated with expression of the HOXA/B locus. Functional experiments demonstrated that FOXC1 contributes to a block in...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2015.07.017

    authors: Somerville TD,Wiseman DH,Spencer GJ,Huang X,Lynch JT,Leong HS,Williams EL,Cheesman E,Somervaille TC

    更新日期:2015-09-14 00:00:00

  • Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma.

    abstract::Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2016.05.020

    authors: Gomes AL,Teijeiro A,Burén S,Tummala KS,Yilmaz M,Waisman A,Theurillat JP,Perna C,Djouder N

    更新日期:2016-07-11 00:00:00

  • Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.

    abstract::The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1(+) stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2015.10.003

    authors: Hayakawa Y,Ariyama H,Stancikova J,Sakitani K,Asfaha S,Renz BW,Dubeykovskaya ZA,Shibata W,Wang H,Westphalen CB,Chen X,Takemoto Y,Kim W,Khurana SS,Tailor Y,Nagar K,Tomita H,Hara A,Sepulveda AR,Setlik W,Gershon MD,

    更新日期:2015-12-14 00:00:00

  • Dragging ras back in the ring.

    abstract::Ras proteins play a major role in human cancers but have not yielded to therapeutic attack. Ras-driven cancers are among the most difficult to treat and often excluded from therapies. The Ras proteins have been termed "undruggable," based on failures from an era in which understanding of signaling transduction, feedba...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.ccr.2014.02.017

    authors: Stephen AG,Esposito D,Bagni RK,McCormick F

    更新日期:2014-03-17 00:00:00

  • VEGF-Mediated Induction of PRD1-BF1/Blimp1 Expression Sensitizes Tumor Vasculature to Oncolytic Virus Infection.

    abstract::Oncolytic viruses designed to attack malignant cells can in addition infect and destroy tumor vascular endothelial cells. We show here that this expanded tropism of oncolytic vaccinia virus to the endothelial compartment is a consequence of VEGF-mediated suppression of the intrinsic antiviral response. VEGF/VEGFR2 sig...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2015.06.009

    authors: Arulanandam R,Batenchuk C,Angarita FA,Ottolino-Perry K,Cousineau S,Mottashed A,Burgess E,Falls TJ,De Silva N,Tsang J,Howe GA,Bourgeois-Daigneault MC,Conrad DP,Daneshmand M,Breitbach CJ,Kirn DH,Raptis L,Sad S,Atkins H

    更新日期:2015-08-10 00:00:00

  • HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity.

    abstract::HIF-2alpha promotes von Hippel-Lindau (VHL)-deficient renal clear cell carcinoma (RCC) tumorigenesis, while HIF-1alpha inhibits RCC growth. As HIF-1alpha antagonizes c-Myc function, we hypothesized that HIF-2alpha might enhance c-Myc activity. We demonstrate here that HIF-2alpha promotes cell-cycle progression in hypo...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2007.02.006

    authors: Gordan JD,Bertout JA,Hu CJ,Diehl JA,Simon MC

    更新日期:2007-04-01 00:00:00

  • Targeting the lncRNA SAMMSON Reveals Metabolic Vulnerability in Melanoma.

    abstract::In a recent study, Leucci et al. report a role for the long non-coding RNA SAMMSON in driving mitochondrial function in melanoma. Targeting SAMMSON, the gene of which is frequently co-amplified with MITF, highlights a new cell-type-specific therapeutic vulnerability in melanoma irrespective of BRAF, NRAS, or p53 statu...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccell.2016.04.010

    authors: Goding CR

    更新日期:2016-05-09 00:00:00

  • Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas.

    abstract::Two recurrent mutations, K27M and G34R/V, within histone variant H3.3 were recently identified in ∼50% of pHGGs. Both mutations define clinically and biologically distinct subgroups of pHGGs. Here, we provide further insight about the dominant-negative effect of K27M mutant H3.3, leading to a global reduction of the r...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccr.2013.10.006

    authors: Bender S,Tang Y,Lindroth AM,Hovestadt V,Jones DT,Kool M,Zapatka M,Northcott PA,Sturm D,Wang W,Radlwimmer B,Højfeldt JW,Truffaux N,Castel D,Schubert S,Ryzhova M,Seker-Cin H,Gronych J,Johann PD,Stark S,Meyer J,Mil

    更新日期:2013-11-11 00:00:00

  • The endless complexity of lymphocyte differentiation and lymphomagenesis: IRF-4 downregulates BCL6 expression.

    abstract::The BCL6 gene is a key factor necessary for formation of germinal centers and is implicated in pathogenesis of diffuse large B cell lymphoma (DLBCL). In this issue of Cancer Cell, Saito and colleagues explore regulation of BCL6 gene expression by CD40-NF-kappaB signaling pathway and show that the IRF4 transcriptional ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.ccr.2007.08.012

    authors: Lossos IS

    更新日期:2007-09-01 00:00:00

  • Turning on a dimer: new insights into MLL chimeras.

    abstract::In this issue of Cancer Cell, demonstrate a novel mechanism for the oncogenic activity of MLL chimeric proteins. By providing coiled-coil or other dimerization domains, the cytoplasmic partners of MLL fusion proteins donate a platform for MLL homodimerization, allowing recruitment of accessory factors needed to activa...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章

    doi:10.1016/s1535-6108(03)00192-2

    authors: Hsu K,Look AT

    更新日期:2003-08-01 00:00:00

  • Large-Scale Characterization of Drug Responses of Clinically Relevant Proteins in Cancer Cell Lines.

    abstract::Perturbation biology is a powerful approach to modeling quantitative cellular behaviors and understanding detailed disease mechanisms. However, large-scale protein response resources of cancer cell lines to perturbations are not available, resulting in a critical knowledge gap. Here we generated and compiled perturbed...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/j.ccell.2020.10.008

    authors: Zhao W,Li J,Chen MM,Luo Y,Ju Z,Nesser NK,Johnson-Camacho K,Boniface CT,Lawrence Y,Pande NT,Davies MA,Herlyn M,Muranen T,Zervantonakis IK,von Euw E,Schultz A,Kumar SV,Korkut A,Spellman PT,Akbani R,Slamon DJ,Gray

    更新日期:2020-12-14 00:00:00

  • Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability.

    abstract::In this study, we show that the formation of polyploidy following sustained mitotic checkpoint activation appears to be preceded by the ubiquitin-dependent proteolysis of hBubR1. In addition, the level of hBubR1 is significantly reduced not only in polyploid cells created by sustained mitotic spindle damage, but also ...

    journal_title:Cancer cell

    pub_type: 杂志文章

    doi:10.1016/s1535-6108(03)00302-7

    authors: Shin HJ,Baek KH,Jeon AH,Park MT,Lee SJ,Kang CM,Lee HS,Yoo SH,Chung DH,Sung YC,McKeon F,Lee CW

    更新日期:2003-12-01 00:00:00