Association of insulin-like growth factor binding protein-3 expression with melanoma progression.


:Previous studies from our laboratory have identified several endothelial cell-associated marker genes implicated in human melanoma metastasis via tumor vasculogenic mimicry. In this study, we used dual model systems composed of melanoma cell lines and clinical melanoma samples to validate the importance of insulin-like growth factor binding protein-3 (IGFBP-3) as a marker involved in disease progression. Gene expression analysis was done using a microarray approach for both primary and metastatic melanoma samples. The expression of IGFBP-3 was decreased using a small interfering RNA (siRNA) knockdown approach and quantified with real-time quantitative reverse transcription-PCR analysis. The expression of insulin-like growth factor binding protein 3 (IGFBP-3) was up-regulated by nearly 16-fold in WM266-4 compared with WM35 cells. A subsequent parallel analysis using freshly isolated primary and metastatic melanoma cell samples and melanoma tissue array confirmed the previous findings. The functional significance of IGFBP-3 in melanoma invasion was further investigated using a siRNA gene knockdown approach, with the expression of IGFBP-3 markedly reduced. Additionally, siRNA knockdown resulted in a significant reduction in cell motility, migration, and invasive capacity of WM266-4 cells in vitro. These results strongly suggest that IGFBP-3 expression may be a vital cell motility, migration, and proliferation factor necessary for melanoma metastasis and is an important biomarker in human melanoma.


Mol Cancer Ther


Xi Y,Nakajima G,Hamil T,Fodstad O,Riker A,Ju J




Has Abstract


2006-12-01 00:00:00














  • Tivantinib (ARQ 197) exhibits antitumor activity by directly interacting with tubulin and overcomes ABC transporter-mediated drug resistance.

    abstract::Tivantinib (ARQ197) was first reported as a highly selective inhibitor of c-MET and is currently being investigated in a phase III clinical trial. However, as recently reported by us and another group, tivantinib showed cytotoxic activity independent of cellular c-MET status and also disrupted microtubule dynamics. To...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Aoyama A,Katayama R,Oh-Hara T,Sato S,Okuno Y,Fujita N

    更新日期:2014-12-01 00:00:00

  • Cis-dichlorodiammineplatinum upregulates angiotensin II type 1 receptors through reactive oxygen species generation and enhances VEGF production in bladder cancer.

    abstract::We previously reported that angiotensin II type 1 receptor (AT1R) antagonists enhanced the cytotoxity of cis-dichlorodiammineplatinum (CDDP) in a bladder cancer xenograft model. To elucidate the synergistic mechanism, we investigated whether reactive oxygen species (ROS) generation induced by CDDP may affect the regul...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Tanaka N,Miyajima A,Kosaka T,Shirotake S,Hasegawa M,Kikuchi E,Oya M

    更新日期:2010-11-01 00:00:00

  • Targeting CXCR2 enhances chemotherapeutic response, inhibits mammary tumor growth, angiogenesis, and lung metastasis.

    abstract::Breast cancer is one of the leading causes of cancer deaths among females. Many challenges exist in the current management of advanced stage breast cancer as there are fewer recognized therapeutic strategies, often because of therapy resistance. How breast cancer cells evade chemotherapy and the underlying mechanism r...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Sharma B,Nawandar DM,Nannuru KC,Varney ML,Singh RK

    更新日期:2013-05-01 00:00:00

  • (-)-Gossypol acts directly on the mitochondria to overcome Bcl-2- and Bcl-X(L)-mediated apoptosis resistance.

    abstract::Aberrant overexpression of antiapoptotic members of the Bcl-2 protein family, including Bcl-2 and Bcl-X(L), contributes to malignant transformation and subsequent resistance to traditional chemotherapeutics. Thus, these proteins represent attractive targets for novel anticancer agents. The small molecule, gossypol, wa...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Oliver CL,Miranda MB,Shangary S,Land S,Wang S,Johnson DE

    更新日期:2005-01-01 00:00:00

  • U3-1402, a Novel HER3-Targeting Antibody-Drug Conjugate, for the Treatment of Colorectal Cancer.

    abstract::HER3 is overexpressed in several cancers, including colorectal cancer. Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits have not been reported. U3-1402 is a novel HER3-antibody-drug conjugate (ADC) composed of the HER3 antibody patritumab and a novel topoisomerase I in...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Koganemaru S,Kuboki Y,Koga Y,Kojima T,Yamauchi M,Maeda N,Kagari T,Hirotani K,Yasunaga M,Matsumura Y,Doi T

    更新日期:2019-11-01 00:00:00

  • Penta-1,2,3,4,6-O-galloyl-beta-D-glucose induces p53 and inhibits STAT3 in prostate cancer cells in vitro and suppresses prostate xenograft tumor growth in vivo.

    abstract::Penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG) is a naturally occurring gallotannin from some Oriental herbs. Several cell culture studies suggested a potential for PGG as a novel agent for the chemoprevention and treatment of cancer. Here, we investigated the cell death signaling mechanisms induced by PGG in human pr...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Hu H,Lee HJ,Jiang C,Zhang J,Wang L,Zhao Y,Xiang Q,Lee EO,Kim SH,Lü J

    更新日期:2008-09-01 00:00:00

  • Phage Display-Derived Peptide-Based Dual-Modality Imaging Probe for Bladder Cancer Diagnosis and Resection Postinstillation: A Preclinical Study.

    abstract::Bladder cancer is a common human malignancy. Conventional ultrasound and white-light cystoscopy are often used for bladder cancer diagnosis and resection, but insufficient specificity results in a high bladder cancer recurrence rate. New strategies for the diagnosis and resection of bladder cancer are needed. In this ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Peng L,Shang W,Guo P,He K,Wang H,Han Z,Jiang H,Tian J,Wang K,Xu W

    更新日期:2018-10-01 00:00:00

  • Cell-penetrating TAT-FOXO3 fusion proteins induce apoptotic cell death in leukemic cells.

    abstract::FOXO proteins are Akt-regulated transcription factors involved in the control of cell cycle, DNA repair, stress defense, apoptosis, and tumor suppression. We reported that plasmid-based overexpression of constitutively active FOXO3 in cells from chronic lymphocytic leukemia (CLL) reduced their survival, suggesting tha...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Essafi M,Baudot AD,Mouska X,Cassuto JP,Ticchioni M,Deckert M

    更新日期:2011-01-01 00:00:00

  • The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates the Activity of p53-Inducing Cytotoxic Agents.

    abstract::p53 is a critical tumor suppressor and is the most frequently inactivated gene in human cancer. Inhibition of the interaction of p53 with its negative regulator MDM2 represents a promising clinical strategy to treat p53 wild-type tumors. AMG 232 is a potential best-in-class inhibitor of the MDM2-p53 interaction and is...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Canon J,Osgood T,Olson SH,Saiki AY,Robertson R,Yu D,Eksterowicz J,Ye Q,Jin L,Chen A,Zhou J,Cordover D,Kaufman S,Kendall R,Oliner JD,Coxon A,Radinsky R

    更新日期:2015-03-01 00:00:00

  • Dibenzophenanthridines as inhibitors of glutaminase C and cancer cell proliferation.

    abstract::One hallmark of cancer cells is their adaptation to rely upon an altered metabolic scheme that includes changes in the glycolytic pathway, known as the Warburg effect, and elevated glutamine metabolism. Glutaminase, a mitochondrial enzyme, plays a key role in the metabolism of glutamine in cancer cells, and its inhibi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Katt WP,Ramachandran S,Erickson JW,Cerione RA

    更新日期:2012-06-01 00:00:00

  • A new nonestrogenic steroidal inhibitor of 17β-hydroxysteroid dehydrogenase type I blocks the estrogen-dependent breast cancer tumor growth induced by estrone.

    abstract::17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) converts estrone (E1) into estradiol (E2) and is expressed in many steroidogenic tissues and breast cancer cell lines. Because the potent estrogen E2 stimulates the growth and development of hormone-dependent diseases, inhibition of the final step of E2 synthesis is c...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Ayan D,Maltais R,Roy J,Poirier D

    更新日期:2012-10-01 00:00:00

  • z-Guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, inhibits angiogenesis in vitro and in vivo.

    abstract::Our previous studies have shown that z-guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, inhibits the growth of human prostate cancer cells by causing apoptosis. We now report a novel response to z-guggulsterone involving the inhibition of angiogenesis in vitro and in vivo. The z-guggu...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Xiao D,Singh SV

    更新日期:2008-01-01 00:00:00

  • EGFR and RB1 as Dual Biomarkers in HPV-Negative Head and Neck Cancer.

    abstract::Clinical decision making for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and anatomic location, with few validated biomarkers. The epidermal growth factor receptor (EGFR) is an important therapeutic target, but its value in guiding therapeu...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Beck TN,Georgopoulos R,Shagisultanova EI,Sarcu D,Handorf EA,Dubyk C,Lango MN,Ridge JA,Astsaturov I,Serebriiskii IG,Burtness BA,Mehra R,Golemis EA

    更新日期:2016-10-01 00:00:00

  • A comprehensive evaluation of biomarkers predictive of response to PI3K inhibitors and of resistance mechanisms in head and neck squamous cell carcinoma.

    abstract::The PI3K/AKT/mTOR pathway is frequently activated in head and neck squamous cell carcinoma (HNSCC), but pathway inhibition has variable efficacy. Identification of predictive biomarkers and mechanisms of resistance would allow selection of patients most likely to respond and novel therapeutic combinations. The purpose...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Mazumdar T,Byers LA,Ng PK,Mills GB,Peng S,Diao L,Fan YH,Stemke-Hale K,Heymach JV,Myers JN,Glisson BS,Johnson FM

    更新日期:2014-11-01 00:00:00

  • The role of gene body cytosine modifications in MGMT expression and sensitivity to temozolomide.

    abstract::The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is known to play a role in sensitivity to temozolomide. Promoter hypermethylation of MGMT is commonly used to predict low expression levels of MGMT in gliomas, despite observed discordance between promoter methylation and protein levels. Here, we i...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Moen EL,Stark AL,Zhang W,Dolan ME,Godley LA

    更新日期:2014-05-01 00:00:00

  • Biological Role and Therapeutic Targeting of TGF-β3 in Glioblastoma.

    abstract::Transforming growth factor (TGF)-β contributes to the malignant phenotype of glioblastoma by promoting invasiveness and angiogenesis and creating an immunosuppressive microenvironment. So far, TGF-β1 and TGF-β2 isoforms have been considered to act in a similar fashion without isoform-specific function in glioblastoma....

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Seystahl K,Papachristodoulou A,Burghardt I,Schneider H,Hasenbach K,Janicot M,Roth P,Weller M

    更新日期:2017-06-01 00:00:00

  • ZD4054, a specific antagonist of the endothelin A receptor, inhibits tumor growth and enhances paclitaxel activity in human ovarian carcinoma in vitro and in vivo.

    abstract::The autocrine endothelin (ET)-1/endothelin A receptor (ET(A)R) pathway is an important regulator of several processes involved in ovarian cancer progression, and its overexpression is associated with aggressive disease. These features have led to the proposal of the ET(A)R receptor as a potential target for improving ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Rosanò L,Di Castro V,Spinella F,Nicotra MR,Natali PG,Bagnato A

    更新日期:2007-07-01 00:00:00

  • Targeting the PI3K/AKT Pathway Overcomes Enzalutamide Resistance by Inhibiting Induction of the Glucocorticoid Receptor.

    abstract::The PI3K-AKT pathway has pleiotropic effects and its inhibition has long been of interest in the management of prostate cancer, where a compensatory increase in PI3K signaling has been reported following androgen receptor (AR) blockade. Prostate cancer cells can also bypass AR blockade through induction of other hormo...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Adelaiye-Ogala R,Gryder BE,Nguyen YTM,Alilin AN,Grayson AR,Bajwa W,Jansson KH,Beshiri ML,Agarwal S,Rodriguez-Nieves JA,Capaldo B,Kelly K,VanderWeele DJ

    更新日期:2020-07-01 00:00:00

  • UPARANT: a urokinase receptor-derived peptide inhibitor of VEGF-driven angiogenesis with enhanced stability and in vitro and in vivo potency.

    abstract::This work is based on previous evidence showing that chemotactic sequence of the urokinase receptor (uPAR(88-92)) drives angiogenesis in vitro and in vivo in a protease-independent manner, and that the peptide Ac-Arg-Glu-Arg-Phe-NH(2) (RERF) prevents both uPAR(88-92)- and VEGF-induced angiogenesis. New N-acetylated an...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Carriero MV,Bifulco K,Minopoli M,Lista L,Maglio O,Mele L,Di Carluccio G,De Rosa M,Pavone V

    更新日期:2014-05-01 00:00:00

  • Simultaneous targeting of COX-2 and AKT using selenocoxib-1-GSH to inhibit melanoma.

    abstract::Melanoma is a highly metastatic and deadly disease. An agent simultaneously targeting the COX-2, PI3K/Akt, and mitogen-activated protein kinase (MAPK) signaling pathways that are deregulated in up to 70% of sporadic melanomas might be an effective treatment, but no agent of this type exists. To develop a single drug i...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Gowda R,Madhunapantula SV,Desai D,Amin S,Robertson GP

    更新日期:2013-01-01 00:00:00

  • 1,25-dihydroxyvitamin D3 enhances the apoptotic activity of MDM2 antagonist nutlin-3a in acute myeloid leukemia cells expressing wild-type p53.

    abstract::The tumor suppressor p53 is often referred to as "the guardian of the genome" because of its central role in the cellular response to oncogenic stress and prevention of tumor development. Mutations of p53 in acute myeloid leukemia (AML) are rare but resistance to chemotherapy has been reported because of the deregulat...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Thompson T,Andreeff M,Studzinski GP,Vassilev LT

    更新日期:2010-05-01 00:00:00

  • Effects of gefitinib (Iressa) on mammary cancers: preventive studies with varied dosages, combinations with vorozole or targretin, and biomarker changes.

    abstract::The ability of the epidermal growth factor receptor inhibitor gefitinib (Iressa) to prevent/treat methylnitrosourea (MNU)-induced mammary cancers and to modulate biomarkers in female Sprague-Dawley rats was examined. Rats were given a single dose of MNU (75 mg/kg body weight) at 50 days of age. In the prevention studi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Lubet RA,Szabo E,Christov K,Bode AM,Ericson ME,Steele VE,Juliana MM,Grubbs CJ

    更新日期:2008-04-01 00:00:00

  • HGF as a circulating biomarker of onartuzumab treatment in patients with advanced solid tumors.

    abstract::The objective of this study was to evaluate circulating hepatocyte growth factor (cHGF) as a pharmacodynamic biomarker of Met inhibition for onartuzumab (MetMAb, OA5D5v2) in a phase I trial in patients with advanced cancers and a phase II trial in non-small cell lung cancer (NSCLC). The phase I study was a dose escala...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章,随机对照试验


    authors: Penuel E,Li C,Parab V,Burton L,Cowan KJ,Merchant M,Yauch RL,Patel P,Peterson A,Hampton GM,Lackner MR,Hegde PS

    更新日期:2013-06-01 00:00:00

  • Blockade of Rac1 activity induces G1 cell cycle arrest or apoptosis in breast cancer cells through downregulation of cyclin D1, survivin, and X-linked inhibitor of apoptosis protein.

    abstract::Rac1 GTPase regulates a variety of signaling pathways that are implicated in malignant phenotypes. Here, we show that selective inhibition of Rac1 activity by the pharmacologic inhibitor NSC23766 suppressed cell growth in a panel of human breast cancer cell lines, whereas it had little toxicity to normal mammary epith...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Yoshida T,Zhang Y,Rivera Rosado LA,Chen J,Khan T,Moon SY,Zhang B

    更新日期:2010-06-01 00:00:00

  • Chemoprevention of chemically induced skin tumorigenesis by ligand activation of peroxisome proliferator-activated receptor-beta/delta and inhibition of cyclooxygenase 2.

    abstract::Ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and inhibition of cyclooxygenase-2 (COX2) activity by nonsteroidal anti-inflammatory drugs (NSAID) can both attenuate skin tumorigenesis. The present study examined the hypothesis that combining ligand activation of PPARβ/δ with inhibition o...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Zhu B,Bai R,Kennett MJ,Kang BH,Gonzalez FJ,Peters JM

    更新日期:2010-12-01 00:00:00

  • 8-amino-adenosine is a potential therapeutic agent for multiple myeloma.

    abstract:UNLABELLED:Multiple myeloma (MM) is a malignancy of clonal B-cells that accounts for 10% of all hematologic malignancies. We have shown previously that a novel purine analogue, 8-chloro-adenosine, has significant activity for MM in preclinical studies. OBJECTIVE:Using MM cell lines, we investigated the molecular mecha...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Krett NL,Davies KM,Ayres M,Ma C,Nabhan C,Gandhi V,Rosen ST

    更新日期:2004-11-01 00:00:00

  • KLF4 p.A472D Mutation Contributes to Acquired Resistance to Cetuximab in Colorectal Cancer.

    abstract::With the increase of treatment course, resistance to EGFR blockade is inevitable in patients with metastatic colorectal cancer (mCRC). KRAS mutations have been considered to be primary drivers of this resistance; however, the potential function of other genes has not been extensively investigated. This study collected...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Ye S,Hu X,Ni C,Jin W,Xu Y,Chang L,Zhou H,Jiang J,Yang L

    更新日期:2020-03-01 00:00:00

  • The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice.

    abstract::CEP-7055, a fully synthetic, orally active N,N-dimethylglycine ester of CEP-5214, a C3-(isopropylmethoxy)-fused pyrrolocarbazole with potent pan-vascular endothelial growth factor receptor (VEGFR) kinase inhibitory activity, has recently completed phase I clinical trials in cancer patients. These studies evaluated the...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Jones-Bolin S,Zhao H,Hunter K,Klein-Szanto A,Ruggeri B

    更新日期:2006-07-01 00:00:00

  • Development and characterization of a potent immunoconjugate targeting the Fn14 receptor on solid tumor cells.

    abstract::TNF-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor (FGF)-inducible 14 (Fn14) are a TNF superfamily ligand-receptor pair involved in many cellular processes including proliferation, migration, differentiation, inflammation, and angiogenesis. The Fn14 receptor is expressed at relatively low levels i...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Zhou H,Marks JW,Hittelman WN,Yagita H,Cheung LH,Rosenblum MG,Winkles JA

    更新日期:2011-07-01 00:00:00

  • Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide.

    abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells. However, its short half-life, poor delivery, and TRAIL-resistant tumor cells have diminished its clinical efficacy. In this study, we explored whether novel delivery methods will represent new and effective ways to treat gli...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章


    authors: Hingtgen S,Ren X,Terwilliger E,Classon M,Weissleder R,Shah K

    更新日期:2008-11-01 00:00:00