PODXL1 promotes metastasis of the pancreatic ductal adenocarcinoma by activating the C5aR/C5a axis from the tumor microenvironment.

Abstract:

:Pancreatic invasive ductal adenocarcinoma (PDAC) is a representative intractable malignancy under the current cancer therapies, and is considered a scirrhous carcinoma because it develops dense stroma. Both PODXL1, a member of CD34 family molecules, and C5aR, a critical cell motility inducer, have gained recent attention, as their expression was reported to correlate with poor prognosis for patients with diverse origins including PDAC; however, previous studies reported independently on their respective biological significance. Here we demonstrate that PODXL1 is essential for metastasis of PDAC cells through its specific interaction with C5aR. In vitro assay demonstrated that PODXL1 bound to C5aR, which stabilized C5aR protein and recruited it to cancer cell plasma membranes to receive C5a, an inflammatory chemoattractant factor. PODXL1 knockout in PDAC cells abrogated their metastatic property in vivo, emulating the liver metastatic mouse model treated with anti-C5a neutralizing antibody. In molecular studies, PODXL1 triggered EMT on PDAC cells in response to stimulation by C5a, corroborating PODXL1 involvement in PDAC cellular invasive properties via specific interaction with the C5aR/C5a axis. Confirming the molecular assays, histological examination showed coexpression of PODXL1 and C5aR at the invasive front of primary cancer nests as well as in liver metastatic foci of PDAC both in the mouse metastasis model and patient tissues. Hence, the novel direct interaction between PODXL1 and the C5aR/C5a axis may provide a better integrated understanding of PDAC biological characteristics including its tumor microenvironment factors.

journal_name

Neoplasia

authors

Saito K,Iioka H,Maruyama S,Sumardika IW,Sakaguchi M,Kondo E

doi

10.1016/j.neo.2019.09.003

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

1121-1132

issue

12

eissn

1522-8002

issn

1476-5586

pii

S1476-5586(19)30251-9

journal_volume

21

pub_type

杂志文章
  • Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma.

    abstract::Glioblastoma (GBM) represents the most aggressive malignancy of the central nervous system. Increased expression of Angiotensin II Receptor Type 1 (AGTR1) has been associated with proliferative and infiltrative properties of glioma cells. However, the underlying mechanism of AGTR1 upregulation in GBM is still unexplor...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.08.002

    authors: Singh A,Srivastava N,Yadav A,Ateeq B

    更新日期:2020-10-01 00:00:00

  • CTHRC1 acts as a prognostic factor and promotes invasiveness of gastrointestinal stromal tumors by activating Wnt/PCP-Rho signaling.

    abstract::Gastrointestinal stromal tumors (GISTs) are the major gastrointestinal mesenchymal tumors with a variable malignancy ranging from a curable disorder to highly malignant sarcomas. Metastasis and recurrence are the main causes of death in GIST patients. To further explore the mechanism of metastasis and to more accurate...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.03.001

    authors: Ma MZ,Zhuang C,Yang XM,Zhang ZZ,Ma H,Zhang WM,You H,Qin W,Gu J,Yang S,Cao H,Zhang ZG

    更新日期:2014-03-01 00:00:00

  • Neutralization of tumor necrosis factor bioactivity ameliorates urethane-induced pulmonary oncogenesis in mice.

    abstract::Tumor necrosis factor (TNF) has been implicated in inflammation-associated tumor progression. Although multiple reports identified a role for TNF signaling in established cancers, few studies have assessed the impact of TNF blockade on early tumor formation promotion. We aimed at exploring the effects of TNF neutraliz...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.111224

    authors: Karabela SP,Kairi CA,Magkouta S,Psallidas I,Moschos C,Stathopoulos I,Zakynthinos SG,Roussos C,Kalomenidis I,Stathopoulos GT

    更新日期:2011-12-01 00:00:00

  • Valproic acid, an antiepileptic drug with histone deacetylase inhibitory activity, potentiates the cytotoxic effect of Apo2L/TRAIL on cultured thoracic cancer cells through mitochondria-dependent caspase activation.

    abstract::Inhibitors of histone deacetylases have been shown to enhance the sensitivity of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand TRAIL-mediated cytotoxicity. Valproic acid (VA), a commonly used antiepileptic agent whose pharmacokinetics and toxicity profiles are well described, is a histone dea...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.05823

    authors: Ziauddin MF,Yeow WS,Maxhimer JB,Baras A,Chua A,Reddy RM,Tsai W,Cole GW Jr,Schrump DS,Nguyen DM

    更新日期:2006-06-01 00:00:00

  • Nilotinib Enhances Tumor Angiogenesis and Counteracts VEGFR2 Blockade in an Orthotopic Breast Cancer Xenograft Model with Desmoplastic Response.

    abstract::Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted therapies predominantly affect nascent, immature tumor vessels. Since platelet-derived growth factor receptor (PDGFR) blockade inhibits vessel maturation and thus increases the amount of immature tumor vessels, we evaluated whether the combined P...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.08.009

    authors: Zafarnia S,Bzyl-Ibach J,Spivak I,Li Y,Koletnik S,Doleschel D,Rix A,Pochon S,Tardy I,Koyadan S,van Zandvoort M,Palmowski M,Kiessling F,Lederle W

    更新日期:2017-11-01 00:00:00

  • Combination of endostatin and a protein kinase Calpha DNA enzyme improves the survival of rats with malignant glioma.

    abstract::Malignant gliomas are refractory to conventional therapies, including surgery, radiotherapy and chemotherapy. Thus, a variety of therapies such as the inhibition of angiogenesis and signal transduction pathways have been attempted. In the present study, we have evaluated the combined effect of endostatin, an inhibitor...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900271

    authors: Sorensen DR,Leirdal M,Iversen PO,Sioud M

    更新日期:2002-11-01 00:00:00

  • 15-lipoxygenase-1 expression upregulates and activates insulin-like growth factor-1 receptor in prostate cancer cells.

    abstract::We previously discovered that a fat-metabolizing enzyme, 15-lipoxygenase-1 (15-LO-1), is high in human prostate cancer (PCa) and correlates with disease progression. The biologic link between the aberrant 15-LO-1/linoleic acid (LA) metabolism and fat (which is a rich source of growth factors) in PCa is unknown. Theref...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/s1476-5586(04)80052-6

    authors: Kelavkar UP,Cohen C

    更新日期:2004-01-01 00:00:00

  • GALNT6 Stabilizes GRP78 Protein by O-glycosylation and Enhances its Activity to Suppress Apoptosis Under Stress Condition.

    abstract::We previously reported that overexpression of an O-type glycosyltransferase, GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) played critical roles in mammary carcinogenesis. To further investigate the biological function of GALNT6, we screened a substrate protein(s) of GALNT6 using a VVA (Vicia villosa agglut...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2016.11.007

    authors: Lin J,Chung S,Ueda K,Matsuda K,Nakamura Y,Park JH

    更新日期:2017-01-01 00:00:00

  • Inhibitors of GLUT/SLC2A Enhance the Action of BCNU and Temozolomide against High-Grade Gliomas.

    abstract::Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glu...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.02.009

    authors: Azzalin A,Nato G,Parmigiani E,Garello F,Buffo A,Magrassi L

    更新日期:2017-04-01 00:00:00

  • Molecular concepts analysis links tumors, pathways, mechanisms, and drugs.

    abstract::Global molecular profiling of cancers has shown broad utility in delineating pathways and processes underlying disease, in predicting prognosis and response to therapy, and in suggesting novel treatments. To gain further insights from such data, we have integrated and analyzed a comprehensive collection of "molecular ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07292

    authors: Rhodes DR,Kalyana-Sundaram S,Tomlins SA,Mahavisno V,Kasper N,Varambally R,Barrette TR,Ghosh D,Varambally S,Chinnaiyan AM

    更新日期:2007-05-01 00:00:00

  • Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma.

    abstract::Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-sc...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.111574

    authors: Yang HW,Kim TM,Song SS,Shrinath N,Park R,Kalamarides M,Park PJ,Black PM,Carroll RS,Johnson MD

    更新日期:2012-01-01 00:00:00

  • Characterizing tumors using metabolic imaging: PET imaging of cellular proliferation and steroid receptors.

    abstract::Treatment decisions in oncology are increasingly guided by information on the biologic characteristics of tumors. Currently, patient-specific information on tumor biology is obtained from the analysis of biopsy material. Positron emission tomography (PET) provides quantitative estimates of regional biochemistry and re...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章,评审

    doi:10.1038/sj.neo.7900075

    authors: Mankoff DA,Dehdashti F,Shields AF

    更新日期:2000-01-01 00:00:00

  • Role of the TMPRSS2-ERG gene fusion in prostate cancer.

    abstract::TMPRSS2-ERG gene fusions are the predominant molecular subtype of prostate cancer. Here, we explored the role of TMPRSS2-ERG gene fusion product using in vitro and in vivo model systems. Transgenic mice expressing the ERG gene fusion product under androgen-regulation develop mouse prostatic intraepithelial neoplasia (...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07822

    authors: Tomlins SA,Laxman B,Varambally S,Cao X,Yu J,Helgeson BE,Cao Q,Prensner JR,Rubin MA,Shah RB,Mehra R,Chinnaiyan AM

    更新日期:2008-02-01 00:00:00

  • A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma.

    abstract::Melanomas are highly radioresistant tumors, mainly due to efficient DNA double-strand break (DSB) repair. Dbait (which stands for DNA strand break bait) molecules mimic DSBs and trap DNA repair proteins, thereby inhibiting repair of DNA damage induced by radiation therapy (RT). First, the cytotoxic efficacy of Dbait i...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.08.008

    authors: Biau J,Devun F,Jdey W,Kotula E,Quanz M,Chautard E,Sayarath M,Sun JS,Verrelle P,Dutreix M

    更新日期:2014-10-23 00:00:00

  • VEGFR3 inhibition chemosensitizes ovarian cancer stemlike cells through down-regulation of BRCA1 and BRCA2.

    abstract::In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor rece...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.04.003

    authors: Lim JJ,Yang K,Taylor-Harding B,Wiedemeyer WR,Buckanovich RJ

    更新日期:2014-04-01 00:00:00

  • Radiocurability is associated with interstitial fluid pressure in human tumor xenografts.

    abstract::Interstitial fluid pressure (IFP) has been shown to be an independent prognostic parameter for disease-free survival in cervical carcinoma patients treated with radiation therapy. However, the underlying mechanisms are not fully understood. The main aims of this study were to investigate whether tumor radiocurability ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.91152

    authors: Rofstad EK,Gaustad JV,Brurberg KG,Mathiesen B,Galappathi K,Simonsen TG

    更新日期:2009-11-01 00:00:00

  • Transgenic expression of Sag/Rbx2 E3 causes early stage tumor promotion, late stage cytogenesis and acinar loss in the Kras-PDAC model.

    abstract::SAG (Sensitive to Apoptosis Gene), also known as RBX2 or ROC2, is a RING component of CRL (Cullin-RING ligase), required for its activity. Our previous studies showed that Sag/Rbx2 co-operated with Kras or Pten loss to promote tumorigenesis in the lung and prostate, respectively, but antagonized Kras to inhibit skin t...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.03.002

    authors: Zhang Q,Wei D,Tan M,Li H,Morgan MA,Sun Y

    更新日期:2020-04-24 00:00:00

  • Generation and characterization of novel local and metastatic human neuroblastoma variants.

    abstract::Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually arises in the adrenal medulla, and it is characterized by a remarkable heterogeneity in its progression. Most NB patients with an advanced disease have massive bone marrow infiltration at diagnosis. Lung metastasis represent...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.08402

    authors: Nevo I,Sagi-Assif O,Edry Botzer L,Amar D,Maman S,Kariv N,Leider-Trejo LE,Savelyeva L,Schwab M,Yron I,Witz IP

    更新日期:2008-08-01 00:00:00

  • Tumor angiogenesis phenotyping by nanoparticle-facilitated magnetic resonance and near-infrared fluorescence molecular imaging.

    abstract::One of the challenges of tailored antiangiogenic therapy is the ability to adequately monitor the angiogenic activity of a malignancy in response to treatment. The α(v)β(3) integrin, highly overexpressed on newly formed tumor vessels, has been successfully used as a target for Arg-Gly-Asp (RGD)-functionalized nanopart...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.121148

    authors: Jarzyna PA,Deddens LH,Kann BH,Ramachandran S,Calcagno C,Chen W,Gianella A,Dijkhuizen RM,Griffioen AW,Fayad ZA,Mulder WJ

    更新日期:2012-10-01 00:00:00

  • Clinical implications of promoter hypermethylation in RASSF1A and MGMT in retinoblastoma.

    abstract::We investigated the epigenetic silencing and genetic changes of the RAS-associated domain family 1A (RASSF1A) gene and the O6-methylguanine-DNA methyltransferase (MGMT) gene in retinoblastoma. We extracted DNA from microdissected tumor and normal retina tissues of the same patient in 68 retinoblastoma cases. Promoter ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04565

    authors: Choy KW,Lee TC,Cheung KF,Fan DS,Lo KW,Beaverson KL,Abramson DH,Lam DS,Yu CB,Pang CP

    更新日期:2005-03-01 00:00:00

  • Gene expression signature for spontaneous cancer regression in melanoma pigs.

    abstract::Incomplete spontaneous regression of melanoma is common. However, complete melanoma regression is still a very rare phenomenon. Because melanoma is the most immunogenic human malignancy, the mechanisms leading to regression, based on accumulative evidence, are the host's immune responses. Unfortunately, therapies aimi...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.08344

    authors: Rambow F,Piton G,Bouet S,Leplat JJ,Baulande S,Marrau A,Stam M,Horak V,Vincent-Naulleau S

    更新日期:2008-07-01 00:00:00

  • CF101, an agonist to the A3 adenosine receptor, enhances the chemotherapeutic effect of 5-fluorouracil in a colon carcinoma murine model.

    abstract::NF-kappaB and the upstream kinase PKB/Akt are highly expressed in chemoresistance tumor cells and may hamper the apoptotic pathway. CF101, a specific agonist to the A3 adenosine receptor (A3AR), inhibits the development of colon carcinoma growth in cell cultures and xenograft murine models. Because CF101 has been show...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04364

    authors: Bar-Yehuda S,Madi L,Silberman D,Gery S,Shkapenuk M,Fishman P

    更新日期:2005-01-01 00:00:00

  • Multitargeted low-dose GLAD combination chemoprevention: a novel and promising approach to combat colon carcinogenesis.

    abstract::Preclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD) are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemo...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.13282

    authors: Mohammed A,Janakiram NB,Brewer M,Vedala K,Steele VE,Rao CV

    更新日期:2013-05-01 00:00:00

  • Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo.

    abstract::A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, and could elucidate temporal dynamics and immune regulation at differe...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900204

    authors: Ponomarev V,Doubrovin M,Lyddane C,Beresten T,Balatoni J,Bornman W,Finn R,Akhurst T,Larson S,Blasberg R,Sadelain M,Tjuvajev JG

    更新日期:2001-11-01 00:00:00

  • Extracellular Acidosis Modulates the Expression of Epithelial-Mesenchymal Transition (EMT) Markers and Adhesion of Epithelial and Tumor Cells.

    abstract::Epithelial-to-mesenchymal transition (EMT) is an important process of tumor progression associated with increased metastatic potential. EMT can be activated by external triggers such as cytokines or metabolic parameters (e.g. hypoxia). Since extracellular acidosis is a common finding in tumors, the aim of the study is...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.03.004

    authors: Riemann A,Rauschner M,Gießelmann M,Reime S,Haupt V,Thews O

    更新日期:2019-05-01 00:00:00

  • Comprehensive Investigation of miRNome Identifies Novel Candidate miRNA-mRNA Interactions Implicated in T-Cell Acute Lymphoblastic Leukemia.

    abstract::T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy originating from T-cell precursors. The genetic landscape of T-ALL has been largely characterized by next-generation sequencing. Yet, the transcriptome of miRNAs (miRNome) of T-ALL has been less extensively studied. Using small RNA sequencing, we ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.01.004

    authors: Dawidowska M,Jaksik R,Drobna M,Szarzyńska-Zawadzka B,Kosmalska M,Sędek Ł,Machowska L,Lalik A,Lejman M,Ussowicz M,Kałwak K,Kowalczyk JR,Szczepański T,Witt M

    更新日期:2019-03-01 00:00:00

  • GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche.

    abstract::Our recent studies have shown that annexin II, expressed on the cell surface of osteoblasts, plays an important role in the adhesion of hematopoietic stem cells (HSCs) to the endosteal niche. Similarly, prostate cancer (PCa) cells express the annexin II receptor and seem to use the stem cell niche for homing to the bo...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.91384

    authors: Shiozawa Y,Pedersen EA,Patel LR,Ziegler AM,Havens AM,Jung Y,Wang J,Zalucha S,Loberg RD,Pienta KJ,Taichman RS

    更新日期:2010-02-01 00:00:00

  • Detection of hypoxia in human brain tumor xenografts using a modified comet assay.

    abstract::We used the standard comet assay successfully to generate in vitro dose-response curves under oxic and hypoxic conditions. We then made mixtures of cells that had been irradiated with 3 and 9 Gy of X-rays to simulate two subpopulations in a tumor, but efforts to accurately detect and quantify the subpopulations using ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/S1476-5586(03)80022-2

    authors: Wang J,Klem J,Wyrick JB,Ozawa T,Cunningham E,Golinveaux J,Allen MJ,Lamborn KR,Deen DF

    更新日期:2003-07-01 00:00:00

  • Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors.

    abstract::The epidermal growth factor receptor (EGFR) has been targeted for inhibition using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in outcome in subsets of patients with head and neck, lung, and colorectal carcinomas. We have previously found that EGFR stability plays a key role in cell survival...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.12986

    authors: Ahsan A,Ramanand SG,Whitehead C,Hiniker SM,Rehemtulla A,Pratt WB,Jolly S,Gouveia C,Truong K,Van Waes C,Ray D,Lawrence TS,Nyati MK

    更新日期:2012-08-01 00:00:00

  • Surface expression of precursor N-cadherin promotes tumor cell invasion.

    abstract::The expression of N-cadherin (NCAD) has been shown to correlate with increased tumor cell motility and metastasis. However, NCAD-mediated adhesion is a robust phenomenon and therefore seems to be inconsistent with the "release" from intercellular adhesion required for invasion. We show that in the most invasive melano...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.10954

    authors: Maret D,Gruzglin E,Sadr MS,Siu V,Shan W,Koch AW,Seidah NG,Del Maestro RF,Colman DR

    更新日期:2010-12-01 00:00:00