Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and Hedgehog signaling activation.

Abstract:

:Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galectin-1 (Gal1) is highly expressed in PDAC stroma, but its roles there have not been studied. Here we report functions and molecular pathways of Gal1 that mediate its oncogenic properties in this setting. Genetic ablation of Gal1 in a mouse model of PDAC (EIa-myc mice) dampened tumor progression by inhibiting proliferation, angiogenesis, desmoplasic reaction and by stimulating a tumor-associated immune response, yielding a 20% increase in relative lifesplan. Cellular analyses in vitro and in vivo suggested these effects were mediated through the tumor microenvironment. Importantly, acinar-to-ductal metaplasia, a crucial step for initiation of PDAC, was found to be regulated by Gal1. Mechanistic investigations revealed that Gal1 promoted Hedgehog pathway signaling in PDAC cells and stromal fibroblasts as well as in Ela-myc tumors. Taken together, our findings establish a function for Gal1 in tumor-stroma crosstalk in PDAC and provide a preclinical rationale for Gal1 targeting as a microenvironment-based therapeutic strategy.

journal_name

Cancer Res

journal_title

Cancer research

authors

Martínez-Bosch N,Fernández-Barrena MG,Moreno M,Ortiz-Zapater E,Munné-Collado J,Iglesias M,André S,Gabius HJ,Hwang RF,Poirier F,Navas C,Guerra C,Fernández-Zapico ME,Navarro P

doi

10.1158/0008-5472.CAN-13-3013

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

3512-24

issue

13

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-13-3013

journal_volume

74

pub_type

杂志文章
  • Retinoid feeding, hormone inhibition, and/or immune stimulation and the genesis of carcinogen-induced rat mammary carcinomas.

    abstract::Female Sprague-Dawley rats were treated at 53 days of age with a single intubation of 7,12-dimethylbenzanthracene (DMBA). Three days after carcinogen treatment, the animals were treated with retinyl acetate (RA) (at 3 dietary levels), hormone inhibition (HI) [tamoxifen (1-rho-beta-dimethylaminoethoxyphenyl-trans-1,2-d...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Welsch CW,DeHoog JV

    更新日期:1983-02-01 00:00:00

  • Medullary thyroid carcinoma arises in the absence of prolactin signaling.

    abstract::Prolactin, a pituitary hormone, exerts pleiotropic effects in various cells. These effects are mediated by a membrane receptor highly expressed in many tissues. To analyze prolactin effects on the thyroid gland, we first identified prolactin receptor (PRLR) mRNAs by in situ hybridization. To further evaluate the physi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3937

    authors: Kedzia C,Lacroix L,Ameur N,Ragot T,Kelly PA,Caillou B,Binart N

    更新日期:2005-09-15 00:00:00

  • Nuclear factor-kappaB p65 mediates tumor necrosis factor alpha-induced nuclear translocation of telomerase reverse transcriptase protein.

    abstract::Sustained proliferation of cancer cells requires telomerase to maintain telomeres that regulate chromosomal stability and cellular mitosis. Expression of human telomerase reverse transcriptase (hTERT) catalytic subunit, which modulates telomerase activity, is regulated at both the transcriptional level and via phospho...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Akiyama M,Hideshima T,Hayashi T,Tai YT,Mitsiades CS,Mitsiades N,Chauhan D,Richardson P,Munshi NC,Anderson KC

    更新日期:2003-01-01 00:00:00

  • Preferential expression of the third immunoglobulin-like domain of K-sam product provides keratinocyte growth factor-dependent growth in carcinoma cell lines.

    abstract::Previously, we identified an amplified gene in a stomach cancer cell line, KATO-III, and designated it K-sam. This gene was later found to be identical with a gene for a receptor tyrosine kinase, bek/FGFR2. One of the characteristics of the K-sam gene is structural diversity of its transcripts; K-sam complementary DNA...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ishii H,Hattori Y,Itoh H,Kishi T,Yoshida T,Sakamoto H,Oh H,Yoshida S,Sugimura T,Terada M

    更新日期:1994-01-15 00:00:00

  • In vitro and in vivo cytotoxicity of an anti-osteosarcoma immunotoxin containing pokeweed antiviral protein.

    abstract::Successful treatment of many patients with osteosarcoma requires more effective chemotherapy. Since new agents are needed, we have developed an immunotoxin using TP-3, an IgG2b mAb which recognizes human and canine osteosarcomas and budding capillaries of tumors. The plant hemitoxin, pokeweed antiviral protein (PAP), ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Anderson PM,Meyers DE,Hasz DE,Covalcuic K,Saltzman D,Khanna C,Uckun FM

    更新日期:1995-03-15 00:00:00

  • Melanoma differentiation associated gene-7/interleukin-24 promotes tumor cell-specific apoptosis through both secretory and nonsecretory pathways.

    abstract::Melanoma differentiation associated gene-7/interleukin-24 (Mda-7/IL-24), a novel member of the IL-10 family of cytokines, uniquely displays cancer-specific apoptosis-inducing activity. Positive results in ongoing phase I/II clinical trials have strengthened the possibility of its utilization as a cancer gene therapeut...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-04-0200

    authors: Sauane M,Lebedeva IV,Su ZZ,Choo HT,Randolph A,Valerie K,Dent P,Gopalkrishnan RV,Fisher PB

    更新日期:2004-05-01 00:00:00

  • Lysis of human promyelocytic HL-60 cells by amphotericin B in combination with 2-chloroethyl-1-nitrosoureas: role of the carbamoylating activity of nitrosoureas.

    abstract::The combinations of amphotericin B (AmB) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) or 2-cyclohexyl isocyanate, the carbamoylating decomposition product of CCNU, were more potent in lysing HL-60 cells than the combinations of AmB with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) or 2-chloroethyl isocyana...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Brajtburg J,Elberg S,Schechtman KB,Medoff G

    更新日期:1990-06-01 00:00:00

  • Dynamic imaging of emerging resistance during cancer therapy.

    abstract::One of the greatest challenges in developing therapeutic regimens is the inability to rapidly and objectively assess tumor response due to treatment. Moreover, tumor response to therapeutic intervention in many cases is transient, and progressive alterations within the tumor may mask the effectiveness of an initially ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-3205

    authors: Lee KC,Hall DE,Hoff BA,Moffat BA,Sharma S,Chenevert TL,Meyer CR,Leopold WR,Johnson TD,Mazurchuk RV,Rehemtulla A,Ross BD

    更新日期:2006-05-01 00:00:00

  • Fats and Mets, KRAS-Driven Lipid Dysregulation Affects Metastatic Potential in Pancreatic Cancer.

    abstract::In this issue of Cancer Research, Rozeveld and colleagues present intriguing evidence of the importance of lipid droplets and hormone-sensitive lipase (HSL) in regulating the aggressive nature of pancreatic cancer. Initially demonstrating a dependency of preloaded lipids on an invasive phenotype, the authors then esta...

    journal_title:Cancer research

    pub_type: 评论,杂志文章

    doi:10.1158/0008-5472.CAN-20-3082

    authors: Man J,Pajic M,Joshua AM

    更新日期:2020-11-15 00:00:00

  • Effects of 2'-deoxycoformycin on the metabolism of purines and the survival of malignant cells in a patient with T-cell leukemia.

    abstract::The in vitro effects of deoxyadenosine and an adenosine deaminase inhibitor, deoxycoformycin, on the synthesis of DNA and the metabolism of purines were investigated in human leukemic T-cells. In the presence of 10 microM deoxycoformycin, the synthesis of DNA was completely inhibited by concentrations of deoxyadenosin...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yu AL,Bakay B,Kung FH,Nyhan WL

    更新日期:1981-07-01 00:00:00

  • Transforming growth factor beta induces clustering of HER2 and integrins by activating Src-focal adhesion kinase and receptor association to the cytoskeleton.

    abstract::It has been proposed that cross talk between integrin and growth factor receptor signaling such as ErbB2 (HER2) is required for activation of downstream effectors and ErbB2-mediated mammary tumorigenesis. Here we show that transforming growth factor beta (TGF-beta) induced focal adhesion kinase (FAK)-dependent cluster...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2649

    authors: Wang SE,Xiang B,Zent R,Quaranta V,Pozzi A,Arteaga CL

    更新日期:2009-01-15 00:00:00

  • Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo.

    abstract::Immunophotodiagnosis uses a fluorescence-labeled monoclonal antibody (MAb) that recognizes a tumor-associated antigen to image the fluorescence emitted from the fluorophore-bound MAb that has localized in the tissue. It may be used to diagnose malignant or precancerous lesions, to delineate the margins for tumor resec...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Soukos NS,Hamblin MR,Keel S,Fabian RL,Deutsch TF,Hasan T

    更新日期:2001-06-01 00:00:00

  • The reduction of N-hydroxy-4-acetylaminobiphenyl by the intestinal microflora of the rat.

    abstract::The role of the intestinal flora in the conversion of N-hydroxy-4-acetyl-aminobiphenyl (N-OH-AABP) to 4-acetylaminobiphenyl has been examined. This reaction, which reverses the metabolic activation of the parent carcinogen, can be demonstrated in cultures of some bacteria indigenous to the intestinal microflora. These...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Wheeler LA,Soderberg FB,Goldman P

    更新日期:1975-11-01 00:00:00

  • Plants with potential to enhance significant tumor growth.

    abstract::Of 20,000 plant extracts submitted to the National Cancer Institute antitumor screens from 1960 to 1980, over 95% exhibited inadequate tumor-inhibiting activity or promoted tumor growth. Of these, 50 extracts representing 42 species showed significant levels of tumor growth enhancement compared to controls on the basi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Caldwell ME,Brewer WR

    更新日期:1983-12-01 00:00:00

  • Dominant-negative mutations of the tumor suppressor p53 relating to early onset of glioblastoma multiforme.

    abstract::Previous experiments have suggested that some mutant forms of p53 are able to inactivate the endogenous wild-type p53 protein in a dominant-negative fashion. However, it remains unknown whether tumors with such dominant-negative (transdominant) p53 mutants have a biological significance that is different from that of ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Marutani M,Tonoki H,Tada M,Takahashi M,Kashiwazaki H,Hida Y,Hamada J,Asaka M,Moriuchi T

    更新日期:1999-10-01 00:00:00

  • Ultraviolet B irradiation promotes tumorigenic and metastatic properties in primary cutaneous melanoma via induction of interleukin 8.

    abstract::UV radiation has been shown to play a role in the initiation of human cutaneous melanoma, but its role in the development of malignant melanoma to the metastatic state is not very well defined. Although previous studies have concentrated on the effect of UV-B on the host immune response, the effect of UV-B on the tumo...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Singh RK,Gutman M,Reich R,Bar-Eli M

    更新日期:1995-08-15 00:00:00

  • Aneuploidy-dependent massive deregulation of the cellular transcriptome and apparent divergence of the Wnt/beta-catenin signaling pathway in human rectal carcinomas.

    abstract::To identify genetic alterations underlying rectal carcinogenesis, we used global gene expression profiling of a series of 17 locally advanced rectal adenocarcinomas and 20 normal rectal mucosa biopsies on oligonucleotide arrays. A total of 351 genes were differentially expressed (P < 1.0e-7) between normal rectal muco...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-2533

    authors: Grade M,Ghadimi BM,Varma S,Simon R,Wangsa D,Barenboim-Stapleton L,Liersch T,Becker H,Ried T,Difilippantonio MJ

    更新日期:2006-01-01 00:00:00

  • Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene.

    abstract::Approximately 10% of gastric adenocarcinomas worldwide are associated with human EBV. These carcinomas generally do not express the latent membrane protein 1 (LMP1), the major known EBV oncogene. Recently, another EBV gene [ie., BARF1 (BamHI A rightward open reading frame)] was shown to have transforming and immortali...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: zur Hausen A,Brink AA,Craanen ME,Middeldorp JM,Meijer CJ,van den Brule AJ

    更新日期:2000-05-15 00:00:00

  • Requirement of the Na+/H+ exchanger for tumor growth.

    abstract::The Na+/H+ exchanger is involved in a variety of cellular processes, including regulation of intracellular pH and possibly the control of cell growth and proliferation. To study the role of the Na+/H+ exchanger in tumor growth, human sodium proton exchanger-deficient (HSPD) mutants were derived from the human bladder ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rotin D,Steele-Norwood D,Grinstein S,Tannock I

    更新日期:1989-01-01 00:00:00

  • Monoclonal antibodies directed to a disulfated glycosphingolipid, SB1a (GgOse4Cer-II3IV3-bis-sulfate), associated with human hepatocellular carcinoma.

    abstract::Two murine monoclonal antibodies, 2H6G5 (IgM) and 4A9E10 (IgG3), were obtained by using either cultured human hepatocellular carcinoma cells (PLC/PRF/5) or the acidic glycolipid mixture prepared from the same cells as immunogens. The antigen in PLC/PRF/5 cell membranes recognized by both antibodies was identified as a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hiraiwa N,Iida N,Ishizuka I,Itai S,Shigeta K,Kannagi R,Fukuda Y,Imura H

    更新日期:1988-12-01 00:00:00

  • Antagonistic effect of aclarubicin on the cytotoxicity of etoposide and 4'-(9-acridinylamino)methanesulfon-m-anisidide in human small cell lung cancer cell lines and on topoisomerase II-mediated DNA cleavage.

    abstract::The effect of combinations of the anthracycline aclarubicin and the topoisomerase II targeting drugs 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyra noside) (VP-16) and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) was investigated in a clonogenic assay. The cytotoxicity of VP-16 was almos...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Jensen PB,Sørensen BS,Demant EJ,Sehested M,Jensen PS,Vindeløv L,Hansen HH

    更新日期:1990-06-01 00:00:00

  • Cooperation between v-fos and v-rasHA induces autonomous papillomas in transgenic epidermis but not malignant conversion.

    abstract::Transgenic mice have been previously established that express v-rasHa or v-fos exclusively in the epidermis by means of a targeting vector based on the human keratin 1 gene (HK1). Epidermal expression of v-rasHa (HK1.ras) or v-fos (HK1.fos) resulted in hyperplasia, hyperkeratosis, and later, in benign tumors. To asses...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Greenhalgh DA,Quintanilla MI,Orengo CC,Barber JL,Eckhardt JN,Rothnagel JA,Roop DR

    更新日期:1993-11-01 00:00:00

  • Adenoviral E1A function through Myc.

    abstract::The study of DNA tumor viruses has been invaluable in uncovering the cellular nodes and pathways that contribute to oncogenesis. Perhaps one of the best-studied oncoproteins encoded by a DNA tumor virus is adenovirus E1A, which modifies the function of key regulatory proteins such as retinoblastoma (Rb) and the chroma...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-08-3026

    authors: Chakraborty AA,Tansey WP

    更新日期:2009-01-01 00:00:00

  • Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappaB through c-FLIP-L expression.

    abstract::The oncoprotein HER-2/neu is a prosurvival factor, and its overexpression has been correlated with poor prognosis in patients with breast cancer. We report that HER-2 is a new substrate for caspase-8 and that tumor necrosis factor alpha (TNF-alpha) stimulation leads to an early caspase-8-dependent HER-2 cleavage in MC...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-03-2914

    authors: Benoit V,Chariot A,Delacroix L,Deregowski V,Jacobs N,Merville MP,Bours V

    更新日期:2004-04-15 00:00:00

  • Regulation of endogenous murine leukemia virus-related nuclear and cytoplasmic RNA complexity in C57BL/6J mice of increasing age.

    abstract::The nucleotide sequence complexity of murine leukemia virus *MuLV)-related RNA has been measured by RNA-complementary DNA hybridization analysis in nuclear and cytoplasmic RNA isolated from liver and brain of low-leukemia-strain C57BL/6J mice of different ages. In these two tissues, an approximate 1.5- to 2-fold incre...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Florine DL,Ono T,Cutler RG,Getz MJ

    更新日期:1980-03-01 00:00:00

  • Dietary administration of the proapoptotic vitamin E analogue alpha-tocopheryloxyacetic acid inhibits metastatic murine breast cancer.

    abstract::The ability of the vitamin E (RRR-alpha-tocopherol) derivatives alpha-tocopheryl succinate (alpha-TOS) and alpha-tocopheryloxyacetic acid (alpha-TEA) to suppress tumor growth in preclinical animal models has recently led to increased interest in their potential use for treating human cancer. To make the use of these v...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-2403

    authors: Hahn T,Szabo L,Gold M,Ramanathapuram L,Hurley LH,Akporiaye ET

    更新日期:2006-10-01 00:00:00

  • Hyaluronic acid induces osteopontin via the phosphatidylinositol 3-kinase/Akt pathway to enhance the motility of human glioma cells.

    abstract::Hyaluronic acid (HA) binds to cell-surface receptors such as CD44, and seems to be involved in cell adhesion, motility, and tumor progression in brain. To identify gene expression changes that are initiated by HA, we explored human cytokine arrays in U87MG glioma cells and identified osteopontin, a secreted matrix pro...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kim MS,Park MJ,Moon EJ,Kim SJ,Lee CH,Yoo H,Shin SH,Song ES,Lee SH

    更新日期:2005-02-01 00:00:00

  • Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase.

    abstract::We have studied the effects of tamoxifen on the cell cycle kinetics of the endocrine-responsive MCF-7 human breast cancer cells. Tamoxifen inhibits proliferation of MCF-7 cells. The tritiated thymidine labeling index is markedly reduced by tamoxifen, indicating a reduction in the fraction of cells in S phase. Flow cyt...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Osborne CK,Boldt DH,Clark GM,Trent JM

    更新日期:1983-08-01 00:00:00

  • Transglutaminase activity in normal and transformed cells.

    abstract::Transglutaminase activity was determined in normal and transformed paired cell systems. Reduced enzyme activity was found in virus-transformed human and hamster cells and in chemically transformed mouse cells relative to normal counterparts. Most of the enzyme activity was localized in the particulate fraction sedimen...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Birckbichler PJ,Orr GR,Conway E,Patterson MK Jr

    更新日期:1977-05-01 00:00:00

  • RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype.

    abstract::Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is phenotypically distinct from other forms of locally advanced breast cancer. In a previous study, we identified specific genetic alterations of IBC that could account for a highly invasive phenotype. RhoC GTPase was overexpressed in 90...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: van Golen KL,Wu ZF,Qiao XT,Bao LW,Merajver SD

    更新日期:2000-10-15 00:00:00