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
  • Tumor-associated macrophages press the angiogenic switch in breast cancer.

    abstract::The development of a supportive vasculature is essential for tumor progression. In a mouse model of breast cancer, we found that tumor-associated macrophages that are recruited to the tumor just before malignant conversion are essential for the angiogenic switch. These findings establish a causal linkage to explain we...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-0912

    authors: Lin EY,Pollard JW

    更新日期:2007-06-01 00:00:00

  • Total serum cholesterol and triglycerides and risk of breast cancer: a prospective study of 24,329 Norwegian women.

    abstract::The association between total serum cholesterol and triglycerides and the incidence rate of breast cancer has been examined in 242 incident cases of breast cancer that developed among 24,329 Norwegian women during 11-14 years of follow-up. At the time of lipid measurement they were between 35 and 51 years of age. Ther...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Vatten LJ,Foss OP

    更新日期:1990-04-15 00:00:00

  • Cytokine gene expression during the generation of human lymphokine-activated killer cells: early induction of interleukin 1 beta by interleukin 2.

    abstract::Culture of human peripheral blood leukocytes with interleukin 2 (IL-2) stimulates their differentiation into lymphokine-activated killer (LAK) cells, with a broad range of cytotoxicity against fresh tumor cells and tumor cell lines (Grimm et al., J. Exp. Med., 155: 1823-1841, 1982). We chose to utilize a molecular app...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kovacs EJ,Beckner SK,Longo DL,Varesio L,Young HA

    更新日期:1989-02-15 00:00:00

  • High incidence of amplification of the epidermal growth factor receptor gene in human squamous carcinoma cell lines.

    abstract::Southern blot-hybridization analysis of DNAs from human tumors demonstrated amplification of the epidermal growth factor (EGF) receptor gene in 10 of 12 squamous cell carcinoma cell lines tested and in none of 18 tumor cell lines of nonsquamous cell carcinomas. The degree of amplification in the squamous cells varied ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yamamoto T,Kamata N,Kawano H,Shimizu S,Kuroki T,Toyoshima K,Rikimaru K,Nomura N,Ishizaki R,Pastan I

    更新日期:1986-01-01 00:00:00

  • SAS amplification in soft tissue sarcomas.

    abstract::Gene amplification is an important mechanism of increased gene expression in a number of human solid tumors. We have recently identified and cloned sequences from a novel DNA amplification unit in malignant fibrous histiocytoma. The amplified sequences are derived from chromosome 12q13-14 and encode a gene designated ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Smith SH,Weiss SW,Jankowski SA,Coccia MA,Meltzer PS

    更新日期:1992-07-01 00:00:00

  • Radioimmunotherapy for breast cancer using escalating fractionated doses of 131I-labeled chimeric L6 antibody with peripheral blood progenitor cell transfusions.

    abstract::Radioimmunotherapy (RAIT) using a humanized murine monoclonal antibody, chimeric L6 (ChL6), has produced objective tumor reduction in 50% of chemotherapy-refractory patients with metastatic breast cancer in our prior studies. Because myelosuppression limited dose escalation, we evaluated the ability of granulocyte col...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Richman CM,DeNardo SJ,O'Grady LF,DeNardo GL

    更新日期:1995-12-01 00:00:00

  • Antitumor efficacy of PD115934 (NSC 366140) against solid tumors of mice.

    abstract::PD115934 (NSC 366140) is a soluble pyrazoloacridine derivative presently undergoing preclinical toxicology evaluation with the anticipation of Phase I human investigation. The agent displayed both human and murine solid tumor selectivity in vitro in a soft agar disk diffusion assay, relative to its activity against mu...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: LoRusso P,Wozniak AJ,Polin L,Capps D,Leopold WR,Werbel LM,Biernat L,Dan ME,Corbett TH

    更新日期:1990-08-15 00:00:00

  • Factors affecting the sensitivity of T-47D human breast cancer cells to tamoxifen.

    abstract::Cell proliferation kinetics during growth of an estrogen receptor-positive human breast carcinoma cell line, T-47D, was defined, and some factors which modify its response to tamoxifen were investigated in vitro. T-47D cells were estrogen responsive when grown in charcoal-stripped fetal calf serum, but the addition of...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Reddel RR,Murphy LC,Sutherland RL

    更新日期:1984-06-01 00:00:00

  • Vascular endothelial growth factor contributes to the prostate cancer-induced osteoblast differentiation mediated by bone morphogenetic protein.

    abstract::Human prostate cancer has a high predisposition to metastasize to bone, resulting in the formation of osteoblastic metastases. The mechanism through which prostate cancer cells promote osteoblastic lesions is undefined. Vascular endothelial growth factor (VEGF) has been implicated as a mediator of osteoblast activity....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-03-1382

    authors: Dai J,Kitagawa Y,Zhang J,Yao Z,Mizokami A,Cheng S,Nör J,McCauley LK,Taichman RS,Keller ET

    更新日期:2004-02-01 00:00:00

  • Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein.

    abstract::The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Wada H,Mizutani S,Nishimura J,Usuki Y,Kohsaki M,Komai M,Kaneko H,Sakamoto S,Delia D,Kanamaru A

    更新日期:1995-07-15 00:00:00

  • Vitamin E succinate (VES) induces Fas sensitivity in human breast cancer cells: role for Mr 43,000 Fas in VES-triggered apoptosis.

    abstract::Fas (CD95/APO-1) is an important mediator of apoptosis. We show that Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 human breast cancer cells become responsive to anti-Fas (CD95) agonistic antibody-triggered apoptosis after pretreatment or cotreatment with vitamin E succinate (VES; RRR-alpha-tocopheryl succinate). In...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yu W,Israel K,Liao QY,Aldaz CM,Sanders BG,Kline K

    更新日期:1999-02-15 00:00:00

  • Genetic differences in metabolism of benzo(a)pyrene in cultured epidermal and dermal cells of responsive and nonresponsive mice.

    abstract::Genetic differences in metabolism of benzo(a)pyrene (BP) were investigated using cultured epidermal keratinocytes and dermal fibroblasts isolated from four inbred strains of mice: C3H/HeJms and C57BL/6J that are responsive; and DBA/2 and AKR/Jms that are nonresponsive in terms of inducibility of aryl hydrocarbon hydro...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hosomi J,Nemoto N,Kuroki T

    更新日期:1983-08-01 00:00:00

  • Purification and characterization of carcinoembryonic antigen-related antigens in normal adult feces.

    abstract::We tried to purify carcinoembryonic antigen (CEA)-related antigens in normal human feces and found that, besides nonspecific cross-reacting antigen (fecal NCA), there are three other molecular species of CEA-related antigens which have been inclusively called normal fecal antigen (NFA). These were designated normal fe...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kuroki M,Koga Y,Matsuoka Y

    更新日期:1981-02-01 00:00:00

  • MK5 Regulates YAP Stability and Is a Molecular Target in YAP-Driven Cancers.

    abstract::Transcriptional regulator YAP is activated in multiple human cancers and plays critical roles in tumor initiation, progression, metastasis, and drug resistance. However, therapeutic targeting of the Hippo-YAP pathway has been challenging due to its low druggability and limited knowledge of YAP regulation in cancer. He...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-1339

    authors: Seo J,Kim MH,Hong H,Cho H,Park S,Kim SK,Kim J

    更新日期:2019-12-15 00:00:00

  • RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics.

    abstract::The candidate tumor suppressor gene RASSF1A is inactivated in many types of adult and childhood cancers. However, the mechanisms by which RASSF1A exerts its tumor suppressive functions have yet to be elucidated. To this end, we performed a yeast two-hybrid screen to identify novel RASSF1A-interacting proteins in a hum...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-0267

    authors: Dallol A,Agathanggelou A,Fenton SL,Ahmed-Choudhury J,Hesson L,Vos MD,Clark GJ,Downward J,Maher ER,Latif F

    更新日期:2004-06-15 00:00:00

  • Distal Chr 4 harbors a genetic locus (Gct1) fundamental for spontaneous ovarian granulosa cell tumorigenesis in a mouse model.

    abstract::The spontaneous development of juvenile-onset ovarian granulosa cell tumors in mice of the SWXJ-9 recombinant inbred strain is a model for juvenile-type granulosa cell tumors that appear in very young girls. To expedite gene discovery in this mouse model of childhood cancer, we did a gene mapping study with the SWXJ-9...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-2992

    authors: Dorward AM,Shultz KL,Horton LG,Li R,Churchill GA,Beamer WG

    更新日期:2005-02-15 00:00:00

  • Contribution of aflatoxin B1 and hepatitis B virus infection in the induction of liver tumors in ducks.

    abstract::The study of two major risk factors in the development of hepatocellular carcinoma, namely persistent hepatitis virus infection and exposure to dietary aflatoxins, has been hampered by lack of an experimental system. To this end we have used a Pekin duck model to examine the effect of congenital duck hepatitis B virus...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Cova L,Wild CP,Mehrotra R,Turusov V,Shirai T,Lambert V,Jacquet C,Tomatis L,Trépo C,Montesano R

    更新日期:1990-04-01 00:00:00

  • Hybrid resistance to BALB/c plasmacytomas: F1 hybrid anti-MPC-11 immunological responses correlated with resistance to tumor challenge.

    abstract::BALB/cJ X C57BL/10Sn F1 (hereafter called B10F1) hybrids resist challenge with the BALB/c plasmacytoma, MPC-11, by a radiation-sensitive, silica-insensitive mechanism, whereas BALB/cJ X BALB.B F1 (hereafter called BALB.BF1) hybrids are as susceptible to MPC-11 as are homozygous BALB/c mice themselves. To investigate t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Marsili MA,Walker MC,Phillips-Quagliata JM

    更新日期:1986-01-01 00:00:00

  • Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma.

    abstract::Cells lacking the tumor suppressor gene LKB1/STK11 alter their metabolism to match the demands of accelerated growth, leaving them highly vulnerable to stress. However, targeted therapy for LKB1-deficient cancers has yet to be reported. In both Kras/p53/Lkb1 cell lines and a genetically engineered mouse model of Kras/...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-17-0567

    authors: Liu Y,Li Y,Wang X,Liu F,Gao P,Quinn MM,Li F,Merlino AA,Benes C,Liu Q,Gray NS,Wong KK

    更新日期:2017-09-15 00:00:00

  • Lipotropes, immunocompetence, and cancer.

    abstract::Lipotropes (choline, methionine, folic acid, and vitamin B12) are required for normal metabolic function at the cellular and subcellular levels. Deficiencies of any or all of them to a point of influence on methyl group metabolism has a profound effect on synthesis of cellular macromolecules and on cell proliferation....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Newbene PM,Nauss KM,de Camargo JL

    更新日期:1983-05-01 00:00:00

  • Tamoxifen DNA damage detected in human endometrium using accelerator mass spectrometry.

    abstract::This study was aimed to establish whether tamoxifen binds irreversibly to uterine DNA when given to women. Patients were given a single therapeutic dose of [(14)C]tamoxifen citrate orally (20 mg, 0.37 or 1.85 MBq) approximately 18 h prior to hysterectomy or breast surgery. Nonmalignant uterine tissue was separated int...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Martin EA,Brown K,Gaskell M,Al-Azzawi F,Garner RC,Boocock DJ,Mattock E,Pring DW,Dingley K,Turteltaub KW,Smith LL,White IN

    更新日期:2003-12-01 00:00:00

  • Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis.

    abstract::Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is an angiogenic cytokine expressed by many human and animal tumors. Hypoxia often up-regulates VPF/VEGF expression further. To better define the role of VPF/VEGF in tumor biology, we screened tumorigenic lines for those expressing minimal co...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Claffey KP,Brown LF,del Aguila LF,Tognazzi K,Yeo KT,Manseau EJ,Dvorak HF

    更新日期:1996-01-01 00:00:00

  • Translocation and activation of protein kinase C by the plasma cell tumor-promoting alkane pristane.

    abstract::Pristane (2,6,10,14-tetramethylpentadecane) is a C19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Janz S,Gawrisch K,Lester DS

    更新日期:1995-02-01 00:00:00

  • Targeting XRCC1 deficiency in breast cancer for personalized therapy.

    abstract::XRCC1 is a key component of DNA base excision repair, single strand break repair, and backup nonhomologous end-joining pathway. XRCC1 (X-ray repair cross-complementing gene 1) deficiency promotes genomic instability, increases cancer risk, and may have clinical application in breast cancer. We investigated XRCC1 expre...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-2929

    authors: Sultana R,Abdel-Fatah T,Abbotts R,Hawkes C,Albarakati N,Seedhouse C,Ball G,Chan S,Rakha EA,Ellis IO,Madhusudan S

    更新日期:2013-03-01 00:00:00

  • Salmonella promoters preferentially activated inside tumors.

    abstract::Salmonella enterica and avirulent derivatives prefer solid tumors over normal tissue in animal models. The identification of endogenous Salmonella promoters that are preferentially activated in tumors could further our understanding of this phenomenon. Toward this goal, a random library of S. enterica typhimurium 1402...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-0552

    authors: Arrach N,Zhao M,Porwollik S,Hoffman RM,McClelland M

    更新日期:2008-06-15 00:00:00

  • Local delivery of chemotherapy and concurrent external beam radiotherapy prolongs survival in metastatic brain tumor models.

    abstract::Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. However, use of local chemotherapy for metastatic brain tumors has not been defined. We studied the safety and the efficacy of locally delivered chemotherapy with and without concur...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ewend MG,Williams JA,Tabassi K,Tyler BM,Babel KM,Anderson RC,Pinn ML,Brat DJ,Brem H

    更新日期:1996-11-15 00:00:00

  • Sphingosine kinase inhibitors and cancer: seeking the golden sword of Hercules.

    abstract::There is considerable evidence that sphingosine kinases play a key role in cancer progression, which might involve positive selection of cancer cells that have been provided with a survival and growth advantage as a consequence of overexpression of the enzyme. Therefore, inhibitors of sphingosine kinase represent a no...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-11-2364

    authors: Pyne S,Bittman R,Pyne NJ

    更新日期:2011-11-01 00:00:00

  • Microenvironmental regulation of proliferation in multicellular spheroids is mediated through differential expression of cyclin-dependent kinase inhibitors.

    abstract::Multicellular spheroids composed of transformed cells are known to mimic the growth characteristics of tumors and to develop gradients in proliferation with increasing size. This progressive accumulation of quiescent cells is presumably an active process that occurs in response to the microenvironmental stresses that ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-2902-2

    authors: LaRue KE,Khalil M,Freyer JP

    更新日期:2004-03-01 00:00:00

  • Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia.

    abstract::Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-16-1303

    authors: Ding LW,Sun QY,Tan KT,Chien W,Mayakonda A,Yeoh AEJ,Kawamata N,Nagata Y,Xiao JF,Loh XY,Lin DC,Garg M,Jiang YY,Xu L,Lim SL,Liu LZ,Madan V,Sanada M,Fernández LT,Hema Preethi SS,Lill M,Kantarjian HM,Kornblau SM,

    更新日期:2017-01-15 00:00:00

  • Apoptotic and cytostatic farnesyltransferase inhibitors have distinct pharmacology and efficacy profiles in tumor models.

    abstract::BMS-214662 and BMS-225975 are tetrahydrobenzodiazepine-based farnesyltransferase inhibitors (FTIs) that have nearly identical structures and very similar pharmacological profiles associated with farnesyltransferase (FT) inhibition. Despite their similar activity against FT in vitro and in cells, these compounds differ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-03-3849

    authors: Manne V,Lee FY,Bol DK,Gullo-Brown J,Fairchild CR,Lombardo LJ,Smykla RA,Vite GD,Wen ML,Yu C,Wong TW,Hunt JT

    更新日期:2004-06-01 00:00:00