Receptor tyrosine kinases and heparan sulfate proteoglycans: Interplay providing anticancer targeting strategies and new therapeutic opportunities.

Abstract:

:The development of pharmacological and biological inhibitors of receptor tyrosine kinases (RTKs) has changed the treatment paradigm of several neoplastic diseases. However, the occurrence of intrinsic and acquired resistance represents a limit to the efficacy of these drugs even in RTK-addicted cancers. The identification of innovative therapeutic approaches and rationale-based drug combinations remains a primary need to improve patients' outcome. Heparan sulfate proteoglycans (HSPGs) at the cell surface and in the extracellular matrix bind to and modulate the biological activity of a great number of heparan sulfate (HS) binding proteins. The participation of HSPGs as accessory molecules in the growth factor-receptor interactions and mechanism of activation of several RTKs provides the basis for developing alternative therapeutic strategies based on targeting HSPGs by antibodies or HS mimetics to interfere with the aberrant oncogenic signaling implicated in the pathobiology of several tumors. Here, we focus on the FGF-FGFR-HSPG and HGF-Met-HSPG axes as paradigmatic examples of the multiple-level interconnections between RTKs and HSPGs influencing cell signaling, gene expression, drug sensitivity, and promoting a permissive microenvironment for tumor growth and progression. In these reciprocal regulations, the HS degrading enzymes heparanase and endosulfatases play key roles contributing to the high structural complexity and heterogeneity of HS chains as well as to the specificity of their interaction with proteins. Actually, heparanase and endosulfatases represent, in turn, promising therapeutic targets. We also report some studies describing the effects of FGFR and Met inhibitors on the expression of genes encoding HSPGs and related enzymes, and discuss about the potential impact of these effects on drug response. Finally, we argue about the need of in-depth investigation of the role of HSPGs and their modifying enzymes in specific tumor pathologies to exploit the opportunity of combination treatments including HS mimetics or HSPG directed antibodies to improve efficacy of RTK inhibitors and overcome drug resistance.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Lanzi C,Cassinelli G

doi

10.1016/j.bcp.2020.114084

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

114084

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(20)30318-X

journal_volume

178

pub_type

杂志文章,评审
  • Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease.

    abstract::The disturbances of the cholesterol synthesis and metabolism described in Alzheimer's disease (AD) may be both a consequence of the neurodegenerative process and a contributor to the pathogenesis. These putative relationships and their underlying mechanisms are not well understood. The aim of this study was to evaluat...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2012.12.007

    authors: Popp J,Meichsner S,Kölsch H,Lewczuk P,Maier W,Kornhuber J,Jessen F,Lütjohann D

    更新日期:2013-07-01 00:00:00

  • In vivo and in vitro studies on the effects of some phenothiazines and sulpiride on kynurenine metabolism.

    abstract::The effect of 5 consecutive daily i.p. doses of CPZ (5 mg/kg), PZ (10 mg/kg) and PMZ (10 mg/kg) on the activity of kynurenine hydrolase and kynurenine aminotransferase in mouse liver was studied. All three phenothiazines effected an increase in the activity of kynurenine hydrolase per unit weight of liver with CPZ sho...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90105-8

    authors: Mostafa MH,El-Sewedy SM,El-Bassiouni EA,Abdel-Tawab GA

    更新日期:1982-07-01 00:00:00

  • Understanding SOS (Son of Sevenless).

    abstract::Son of Sevenless (SOS) was discovered in Drosophila melanogaster. Essential for normal eye development in Drosophila, SOS has two human homologues, SOS1 and SOS2. The SOS1 gene encodes the Son of Sevenless 1 protein, a Ras and Rac guanine nucleotide exchange factor. This protein is composed of several important domain...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.bcp.2011.07.072

    authors: Pierre S,Bats AS,Coumoul X

    更新日期:2011-11-01 00:00:00

  • Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC.

    abstract::Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreo...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2018.01.026

    authors: Shi L,Hao Z,Zhang S,Wei M,Lu B,Wang Z,Ji L

    更新日期:2018-04-01 00:00:00

  • Gimatecan and other camptothecin derivatives poison Leishmania DNA-topoisomerase IB leading to a strong leishmanicidal effect.

    abstract::The aim of this work is the in vitro and ex vivo assessment of the leishmanicidal activity of camptothecin and three analogues used in cancer therapy: topotecan (Hycantim®), gimatecan (ST1481) and the pro-drug irinotecan (Camptosar®) as well as its active metabolite SN-38 against Leishmania infantum. The activity of c...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2013.02.024

    authors: Prada CF,Alvarez-Velilla R,Balaña-Fouce R,Prieto C,Calvo-Álvarez E,Escudero-Martínez JM,Requena JM,Ordóñez C,Desideri A,Pérez-Pertejo Y,Reguera RM

    更新日期:2013-05-15 00:00:00

  • Entrectinib reverses cytostatic resistance through the inhibition of ABCB1 efflux transporter, but not the CYP3A4 drug-metabolizing enzyme.

    abstract::Entrectinib is a new tyrosine kinase inhibitor that was recently approved for the treatment of ROS1-positive metastatic non-small cell lung cancer (NSCLC). In this study, we aimed to characterize its potential to act as a modulator of pharmacokinetic cytostatic resistance and perpetrator of drug interactions. In accum...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2020.114061

    authors: Vagiannis D,Yu Z,Novotna E,Morell A,Hofman J

    更新日期:2020-08-01 00:00:00

  • Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment.

    abstract::Curcumin (diferuoylmethane), the yellow pigment in the rhizome of tumeric (Curcuma longa), an ingredient of curry spice, is known to exhibit a variety of pharmacological effects including antitumor, antiinflammatory, and antiinfectious activities. Although its precise mode of action remains elusive, curcumin has been ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(97)00251-7

    authors: Sikora E,Bielak-Zmijewska A,Piwocka K,Skierski J,Radziszewska E

    更新日期:1997-10-15 00:00:00

  • Effects of vitamin E deficiency and glutathione depletion on stress protein heme oxygenase 1 mRNA expression in rat liver and kidney.

    abstract::Heme oxygenase 1 (HO-1) is a stress protein and has been suggested to provide defense mechanisms against agents that may induce oxidative injury. Vitamin E (VE) is considered to function as an important cellular antioxidant. Rats were fed a VE-deficient (0E) or a VE-sufficient (10E) diet for 6 weeks and then were intr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(97)00302-x

    authors: Ito K,Yano T,Hagiwara K,Ozasa H,Horikawa S

    更新日期:1997-11-15 00:00:00

  • Sensitization of acute lymphoblastic leukemia cells for LCL161-induced cell death by targeting redox homeostasis.

    abstract::Disturbed redox homeostasis with both elevated reactive oxygen species (ROS) levels and antioxidant defense mechanisms has been reported in acute lymphoblastic leukemia (ALL). We therefore hypothesized that inhibition of pathways responsible for ROS detoxification renders ALL cells more susceptible for cell death. Her...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2016.01.004

    authors: Haß C,Belz K,Schoeneberger H,Fulda S

    更新日期:2016-04-01 00:00:00

  • Comparison of the effects of recently developed alpha 2-adrenergic antagonists with yohimbine and rauwolscine on monoamine synthesis in rat brain.

    abstract::The effects of two recently developed alpha 2-adrenergic antagonists, RX 781094 and WY 26703, on the synthesis of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in rat brain were compared to those of yohimbine, its diastereoisomer rauwolscine, and mianserin. Intraperitoneal administration of these compounds i...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(85)90614-8

    authors: Pettibone DJ,Pfleuger AB,Totaro JA

    更新日期:1985-04-01 00:00:00

  • Andrographolide derivative ameliorates dextran sulfate sodium-induced experimental colitis in mice.

    abstract::The therapeutic efficacy of immunosuppressive agents has been intensively studied for colitis management. We synthesized a series of andrographolide derivatives and reported their structure-activity-relationship and anti-inflammatory activity in our previous studies. Among these derivatives, compound 3b exhibited the ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2019.03.019

    authors: Guo BJ,Liu Z,Ding MY,Li F,Jing M,Xu LP,Wang YQ,Zhang ZJ,Wang Y,Wang D,Zhou GC,Wang Y

    更新日期:2019-05-01 00:00:00

  • Effects of tannic acid on 12-O-tetradecanoylphorbol-13-acetate-induced protein kinase C activation in NIH 3T3 cells.

    abstract::Tannic acid (TA) is a naturally occurring phenol, which has been found to display an antipromotion effect on mouse skin carcinogenesis. In order to explore the molecular mechanism, we have examined the process of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced protein kinase C (PKC) activation, including phorbol es...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90095-e

    authors: Kuo ML,Wu WS,Lee KC,Lin JK

    更新日期:1993-10-19 00:00:00

  • Broad specificity of human phosphoglycerate kinase for antiviral nucleoside analogs.

    abstract::Nucleoside analogs used in antiviral therapies need to be phosphorylated to their tri-phospho counterparts in order to be active on their cellular target. Human phosphoglycerate kinase (hPGK) was recently reported to participate in the last step of phosphorylation of cytidine L-nucleotide derivatives [Krishnan PGE, La...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2004.06.012

    authors: Gallois-Montbrun S,Faraj A,Seclaman E,Sommadossi JP,Deville-Bonne D,Véron M

    更新日期:2004-11-01 00:00:00

  • Prenylated quinolinecarboxylic acid derivative prevents neuronal cell death through inhibition of MKK4.

    abstract::The development of neuroprotective agents is necessary for the treatment of neurodegenerative diseases. Here, we report PQA-11, a prenylated quinolinecarboxylic acid (PQA) derivative, as a potent neuroprotectant. PQA-11 inhibits glutamate-induced cell death and caspase-3 activation in hippocampal cultures, as well as ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2018.10.008

    authors: Ogura M,Kikuchi H,Shakespear N,Suzuki T,Yamaki J,Homma MK,Oshima Y,Homma Y

    更新日期:2019-04-01 00:00:00

  • Autophagy exacerbates caspase-dependent apoptotic cell death after short times of starvation.

    abstract::Autophagy is generally regarded as a mechanism to promote cell survival. However, autophagy can occasionally be the mechanism responsible of cell demise. We have found that a concomitant depletion of glucose, nutrients and growth factors provoked cell death in a variety of cell lines. This death process was contingent...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2015.09.021

    authors: Mattiolo P,Yuste VJ,Boix J,Ribas J

    更新日期:2015-12-15 00:00:00

  • 2,5-Hexanedione modifies skeletal proteins of the red blood cells and increases the binding of hemoglobin to the membrane.

    abstract::The effects of 2,5-hexanedione (2,5 HD) on skeletal proteins of red blood cells (RBCs) were investigated both in vitro (human RBCs) and in vivo in male Sprague-Dawley rats which had been treated with the drug for several days. We found that 2,5 HD induced the following major changes in the electrophoretic pattern of t...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(89)90557-1

    authors: Mallozzi C,Scorza G,Frontali N,Minetti M

    更新日期:1989-08-15 00:00:00

  • Differential regulation of expression of rat hippocampal muscarinic receptor subtypes following fimbria-fornix lesion.

    abstract::Quantitative RNase protection assays were performed to determine the levels of muscarinic receptor subtype (m1-m5) mRNAs in rat hippocampi. Results showed that the m1, m3, and m4 subtype mRNAs were expressed at relatively high levels, but the levels of the m2 and m5 subtype were very low. Three weeks following aspirat...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(97)00074-9

    authors: Zang Z,Creese I

    更新日期:1997-05-09 00:00:00

  • Structural and functional assembly of rat intestinal cytochrome P-450 isozymes. Effects of dietary iron and selenium.

    abstract::We have reported previously that both dietary iron and selenium regulate intestinal cytochrome P-450 content by modulating the synthesis of its prosthetic heme moiety. Whether these elements are required for synthesis and/or viability of its apocytochrome moiety is unknown. We have examined the effects of intraluminal...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(85)90252-7

    authors: Pascoe GA,Correia MA

    更新日期:1985-03-01 00:00:00

  • Modulation by verapamil of vincristine pharmacokinetics and toxicity in mice bearing human tumor xenografts.

    abstract::The effect of the calcium channel blocker verapamil (VRP) on the accumulation and retention of vincristine (VCR) has been examined in mice bearing xenografts of human rhabdomyosarcomas. The tumors were Rh18, moderately sensitive to VCR, and its subline, Rh18/VCR3, selected in vivo for primary resistance to VCR. Admini...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(89)90405-x

    authors: Horton JK,Thimmaiah KN,Houghton JA,Horowitz ME,Houghton PJ

    更新日期:1989-06-01 00:00:00

  • Innovative treatment programs against cancer: II. Nuclear factor-kappaB (NF-kappaB) as a molecular target.

    abstract::Nuclear factor-kappaB (NF-kappaB) activity affects cell survival and determines the sensitivity of cancer cells to cytotoxic agents as well as to ionizing radiation. Preventing the protective function of NF-kappaB may result in chemo- and radio-sensitization of cancer cells. Therefore, NF-kappaB has emerged as one of ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/s0006-2952(98)00224-x

    authors: Waddick KG,Uckun FM

    更新日期:1999-01-01 00:00:00

  • Desulfuration of 6-mercaptopurine. The basis for the paradoxical cytotoxicity of thiopurines in cultured human leukemic cells.

    abstract::The thiopurines have a wide array of effects on purine metabolism, but the primary mechanism of cytotoxicity for both 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) appears to be incorporation of drug into DNA following conversion to the thioguanylate form. In murine leukemic cell lines exposed to a range of thiopur...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90333-r

    authors: Adamson PC,Balis FM,Hawkins ME,Murphy RF,Poplack DG

    更新日期:1993-11-02 00:00:00

  • The metabolism of the xenobiotic triacylglycerols, rac-1- and sn-2- (3-phenoxybenzoyl)-dipalmitoylglycerol, following intravenous administration to the rat.

    abstract::The metabolism of 3-phenoxybenzoic acid (3PBA) in the form of triacylglycerol conjugates was compared with that of non-esterified 3PBA. Three radiolabeled triacylglycerols (rac-1-(3-phenoxy-[ring-14C]-benzoyl)-2,3-dipalmitoylglycerol (1(3PBA)DPG), sn-2-(3-phenoxy-[ring-14C]benzoyl)-1,3-dipalmitoylglycerol (2(3PBA)DPG)...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(98)00196-8

    authors: Haselden JN,Dodds PF,Hutson DH

    更新日期:1998-12-15 00:00:00

  • Ethanol enhancement of ligand-stimulated cAMP production by cultured human placental trophoblasts.

    abstract::Chronic ethanol (EtOH) use during pregnancy can be associated with fetal injury including the fetal alcohol syndrome (FAS). A contributing factor in this fetal injury may be the effect of EtOH on the placenta. In this study, we have examined the effect of in vitro EtOH treatment on adenosine 3':5'-cyclic monophosphate...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90575-4

    authors: Karl PI,Divald A,Fisher SE

    更新日期:1994-10-07 00:00:00

  • Diacylglycerol kinase inhibitor, R59022, potentiates neutrophil oxidase activation by Ca2+-dependent stimuli. Evidence for two separate but convergent pathways.

    abstract::An inhibitor of diacylglycerol kinase, R59022, enhanced activation of the neutrophil oxidase stimulated by the Ca2+-ionophore, A23187 (1 microM), and by N-formyl-methionyl leucyl-phenylalanine (1 microM). The enhancement was reversed by two inhibitors of c-kinase, retinal (10 microM), and gossypol (20 microM). Activat...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(87)90326-1

    authors: Cooke E,Al-Mohanna FA,Hallett MB

    更新日期:1987-10-15 00:00:00

  • Some properties of monoamine oxidase and a semicarbazide sensitive amine oxidase capable of the deamination of 5-hydroxytryptamine from porcine dental pulp.

    abstract::The deamination of 5-hydroxytryptamine, tryptamine and benzylamine by porcine dental pulp membrane preparations is brought about not only by monoamine oxidase, but also by a clorgyline (and deprenyl) resistant), semicarbazide sensitive enzyme. The semicarbazide sensitive enzyme was also inhibited by aminoguanidine, hy...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90127-7

    authors: Norqvist A,Oreland L,Fowler CJ

    更新日期:1982-09-01 00:00:00

  • Formation of the thiol adducts of 4'-(9-acridinylamino)methanesulfon-m-anisidide and their binding to deoxyribonucleic acid.

    abstract::We investigated the interactions of 4'-(9-acridinylamino)methanesulfon-m-anisidide (mAMSA) with thiol-containing compounds and the potential binding of the thiolytic adducts to DNA. All thiols tested (glutathione, cysteine, coenzyme A, 2-mercaptoethanol and lactate dehydrogenase) formed adducts with mAMSA as evidenced...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90319-9

    authors: Wong A,Huang CH,Hwang SM,Prestayko AW,Crooke ST

    更新日期:1986-05-15 00:00:00

  • On the role of thiol groups in the inhibition of liver microsomal Ca2+ sequestration by toxic agents.

    abstract::ATP-dependent Ca2+ sequestration by rat liver microsomes was assayed using three different methods, and characterized with regard to the effect of various inhibitors. When glucose and hexokinase were added in combination to deplete ATP in the incubation, Ca2+ uptake was followed by rapid release of Ca2+ from the micro...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(85)90236-9

    authors: Thor H,Hartzell P,Svensson SA,Orrenius S,Mirabelli F,Marinoni V,Bellomo G

    更新日期:1985-10-15 00:00:00

  • Depletion of cardiac norepinephrine in rats and mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

    abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a commercially available chemical reagent. Although little has been known about its biological effects, recently MPTP has been reported to cause irreversible Parkinson's disease-like symptoms in humans and in monkeys. We describe here another pharmacologic effect ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(84)90593-8

    authors: Fuller RW,Hahn RA,Snoddy HD,Wikel JH

    更新日期:1984-10-01 00:00:00

  • Protein kinase- and staurosporine-dependent induction of neurite outgrowth and plasminogen activator activity in PC12 cells.

    abstract::We analysed how interactions between protein kinase-dependent intracellular signalling pathways were implicated in the control of the production of tissue-type plasminogen activator (tPA) and the generation of neurite outgrowth by PC12 cells. To that aim, cells were treated with agents that interact with the trk recep...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(96)00472-8

    authors: Leprince P,Bonvoisin C,Rogister B,Mazy-Servais C,Moonen G

    更新日期:1996-11-08 00:00:00

  • Differential contribution of metabotropic glutamate receptor 5 common allosteric binding site residues to biased allosteric agonism.

    abstract::Allosteric modulators of metabotropic glutamate receptor subtype 5 (mGlu5) represent an attractive therapeutic strategy for multiple CNS disorders. Chemically distinct mGlu5 positive allosteric modulators (PAMs) that interact with a common binding site can demonstrate biased allosteric agonism relative to the orthoste...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2020.114011

    authors: Sengmany K,Hellyer SD,Christopoulos A,Lapinsky DJ,Leach K,Gregory KJ

    更新日期:2020-07-01 00:00:00