Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases

被引：107
作者：
Varney, Michelle L. [1 ]
Singh, Seema [1 ]
Li, Aihua [1 ]
Mayer-Ezell, Rosemary [2 ]
Bond, Richard [2 ]
Singh, Rakesh K. [1 ]
机构：
[1] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA
[2] Merck Res Labs, Kenilworth, NJ USA
来源：
CANCER LETTERS | 2011年 / 300卷 / 02期
基金：
美国国家卫生研究院;
关键词：
Chemokine; Angiogenesis; Metastasis; Colon cancer; GRANULOCYTE CHEMOTACTIC PROTEIN-2; MALIGNANT-MELANOMA; CARCINOMA-CELLS; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; INTERLEUKIN-8; EXPRESSION; CHEMOKINES; GROWTH; RECEPTORS;
D O I：
10.1016/j.canlet.2010.10.004
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
CXCR1 and CXCR2 are G-protein coupled receptors that have been shown to play important role in tumor growth and metastasis and are prime targets for the development of novel therapeutics Here we report that targeting CXCR2 and CXCR1 activity using orally active small molecule antagonist (SCH-527123 SCH-479833) inhibits human colon cancer liver metastasis mediated by decreased neovascularization and enhanced malignant cell apoptosis There were no differences in primary tumor growth These studies demonstrate the important role of CXCR2/1 in colon cancer metastasis and that inhibition of CXCR2 and CXCR1 small molecule antagonists provides a novel therapeutic strategy (C) 2010 Elsevier Ireland Ltd All rights reserved
引用
收藏
页码：180 / 188
页数：9
相关论文
共 47 条
  • [1] A Role for CXCR2 in Senescence, but What about in Cancer?
    Acosta, Juan C.
    Gil, Jesus
    [J]. CANCER RESEARCH, 2009, 69 (06) : 2167 - 2170
  • [2] The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity
    Addison, CL
    Daniel, TO
    Burdick, MD
    Liu, H
    Ehlert, JE
    Xue, YY
    Buechi, L
    Walz, A
    Richmond, A
    Strieter, RM
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (09) : 5269 - 5277
  • [3] [Anonymous], CA CANC J CLIN
  • [4] Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: Prevention of reperfusion injury
    Bertini, R
    Allegretti, M
    Bizzarri, C
    Moriconi, A
    Locati, M
    Zampella, G
    Cervellera, MN
    Di Cioccio, V
    Cesta, MC
    Galliera, E
    Martinez, FO
    Di Bitondo, R
    Troiani, G
    Sabbatini, V
    D'Anniballe, G
    Anacardio, R
    Cutrin, JC
    Cavalieri, B
    Mainiero, F
    Strippoli, R
    Villa, P
    Di Girolamo, M
    Martin, F
    Gentile, M
    Santoni, A
    Corda, D
    Poli, G
    Mantovani, A
    Ghezzi, P
    Colotta, F
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (32) : 11791 - 11796
  • [5] CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
  • [6] De Larco JE, 2001, CANCER RES, V61, P2857
  • [7] A potential role for interleukin-8 in the metastatic phenotype of breast carcinoma cells
    De Larco, JE
    Wuertz, BRK
    Rosner, KA
    Erickson, SA
    Gamache, DE
    Manivel, JC
    Furcht, LT
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (02) : 639 - +
  • [8] Dhawan P, 2002, J LEUKOCYTE BIOL, V72, P9
  • [9] Discovery of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123):: A potent, orally bioavailable CXCR2/CXCR1 receptor antagonist
    Dwyer, Michael P.
    Yu, Younong
    Chao, Jianping
    Aki, Cynthia
    Chao, Jianhua
    Biju, Purakkattle
    Girijavallabhan, Viyyoor
    Rindgen, Diane
    Bond, Richard
    Mayer-Ezel, Rosemary
    Jakway, James
    Hipkin, R. William
    Fossetta, James
    Gonsiorek, Waldemar
    Bian, Hong
    Fan, Xuedong
    Terminelli, Carol
    Fine, Jay
    Lundell, Daniel
    Merritt, J. Robert
    Rokosz, Laura L.
    Kaiser, Bernd
    Li, Ge
    Wang, Wei
    Stauffer, Tara
    Ozgur, Lynne
    Baldwin, John
    Taveras, Arthur G.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (26) : 7603 - 7606
  • [10] ELI MB, 1999, PATHOBIOLOGY, V67, P12
12345